PMC:3342329 / 16227-19092 JSONTXT

{"project":"test3","denotations":[{"id":"T19582","span":{"begin":1318,"end":1322},"obj":"Protein"},{"id":"T19581","span":{"begin":1318,"end":1322},"obj":"Protein"},{"id":"T7328","span":{"begin":2852,"end":2856},"obj":"Protein"},{"id":"T7327","span":{"begin":2639,"end":2643},"obj":"Protein"},{"id":"T7326","span":{"begin":2513,"end":2517},"obj":"Protein"},{"id":"T7325","span":{"begin":2472,"end":2475},"obj":"Protein"},{"id":"T7324","span":{"begin":2444,"end":2448},"obj":"Protein"},{"id":"T7323","span":{"begin":2405,"end":2408},"obj":"Protein"},{"id":"T7322","span":{"begin":2394,"end":2398},"obj":"Protein"},{"id":"T7321","span":{"begin":2355,"end":2359},"obj":"Protein"},{"id":"T7320","span":{"begin":2272,"end":2276},"obj":"Protein"},{"id":"T7319","span":{"begin":2143,"end":2147},"obj":"Protein"},{"id":"T7318","span":{"begin":2106,"end":2109},"obj":"Protein"},{"id":"T7317","span":{"begin":1981,"end":1985},"obj":"Protein"},{"id":"T7316","span":{"begin":1964,"end":1968},"obj":"Protein"},{"id":"T7315","span":{"begin":1163,"end":1167},"obj":"Protein"},{"id":"T7314","span":{"begin":960,"end":964},"obj":"Protein"},{"id":"T7313","span":{"begin":921,"end":925},"obj":"Protein"},{"id":"T7312","span":{"begin":728,"end":732},"obj":"Protein"},{"id":"T7311","span":{"begin":711,"end":715},"obj":"Protein"},{"id":"T7310","span":{"begin":364,"end":368},"obj":"Protein"},{"id":"T7309","span":{"begin":145,"end":149},"obj":"Protein"},{"id":"T7308","span":{"begin":75,"end":79},"obj":"Protein"},{"id":"T7307","span":{"begin":2852,"end":2856},"obj":"Protein"},{"id":"T7306","span":{"begin":2639,"end":2643},"obj":"Protein"},{"id":"T7305","span":{"begin":2513,"end":2517},"obj":"Protein"},{"id":"T7304","span":{"begin":2472,"end":2475},"obj":"Protein"},{"id":"T7303","span":{"begin":2444,"end":2448},"obj":"Protein"},{"id":"T7302","span":{"begin":2405,"end":2408},"obj":"Protein"},{"id":"T7301","span":{"begin":2394,"end":2398},"obj":"Protein"},{"id":"T7300","span":{"begin":2355,"end":2359},"obj":"Protein"},{"id":"T7299","span":{"begin":2272,"end":2276},"obj":"Protein"},{"id":"T7298","span":{"begin":2143,"end":2147},"obj":"Protein"},{"id":"T7297","span":{"begin":2106,"end":2109},"obj":"Protein"},{"id":"T7296","span":{"begin":1981,"end":1985},"obj":"Protein"},{"id":"T7295","span":{"begin":1964,"end":1968},"obj":"Protein"},{"id":"T7294","span":{"begin":1163,"end":1167},"obj":"Protein"},{"id":"T7293","span":{"begin":960,"end":964},"obj":"Protein"},{"id":"T7292","span":{"begin":921,"end":925},"obj":"Protein"},{"id":"T7291","span":{"begin":728,"end":732},"obj":"Protein"},{"id":"T7290","span":{"begin":711,"end":715},"obj":"Protein"},{"id":"T7289","span":{"begin":364,"end":368},"obj":"Protein"},{"id":"T7288","span":{"begin":145,"end":149},"obj":"Protein"},{"id":"T7287","span":{"begin":75,"end":79},"obj":"Protein"}],"text":"Induction of CD8 T cells and NK Cell Infiltration into Tumor and Spleen of CCR5−/− Mice\nTo investigate whether the inhibition of tumor growth in CCR5−/− mice is related to tumor-specific immune responses, we analyzed the distribution patterns of CD8+ cytotoxic T cell and CD57+ Natural Killer cells in tumor and spleen tissues. By staining the tumor sections from CCR5−/− mice, we found that there was a significant influx of CD8+ cells into the tumor, as well as an increase in the number of infiltrating NK cells (Figure 5A). CD8+ T cells and CD57+ NK cells were spread diffusely throughout the entire sections. To further investigate the differences in the numbers of CD8+ T cells and CD57+ NK cells between CCR5+/+ mice and CCR5−/− mice in immunity-related organ, we also analyzed the CD8 and CD57 reactive cell number in spleen tissues. The number of CD8+ T cells and CD57+ NK cells were higher in the spleen of the CCR5−/− mice than in the spleen of the CCR5+/+ mice (Figure 5B). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in an anti-tumor effect in CCR5−/− mice.\n10.1371/journal.pone.0033747.g005 Figure 5 Induction of the infiltration of CD8+ T cells and NK cells into tumor, and increase in spleen of CCR5−/− mice.\nA and B, Immunolfluorescence analysis was used to determine the expression levels of CD8 (CD8+ cytotoxic T-cell surface marker) and CD57 (NK cell marker) in tumor and spleen sections. The images shown are representative of three separate experiments performed in triplicate. Scale bars indicate 50 µm (A) and 100 µm (B). C and D, Analysis of lymphocyte phenotypes. The tumor and spleen tissues were separated at study termination (Day 31). Flow cytometry analysis was performed using FACSAria flow cytometry, and represent data were shown. Data are means ± S.D. of four experimental animals. To analyze the cell phenotype change in CCR5−/− mice and CCR5+/+ mice by inoculation of the melanoma cell, lymphocytes were isolated from the tumor and spleen tissues. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of CCR5−/− mice tumor tissue were 7.2%, 48.2%, 16.9%, 32.1% and 7.8%, respectively, compared to 2.9%, 11.1%, 2.3%, 0.6% and 3.1% of CCR5+/+ mice (Figure 5C). The lymphocytes that infiltrated the tumor tissue of the CCR5−/− mice also had higher levels of CD19, CD3, CD4, CD8 and CD57 when compared to the CCR5+/+ mice. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of the CCR5−/− mice spleen were 61.3%, 33.4%, 17.6%, 9.2% and 0.6%, respectively compared to 38.3%, 5.9%, 4.0%, 1.0% and 3.9% of the CCR5+/+ mice (Figure 5D). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in the inhibition of tumor growth in CCR5−/− mice."}

{"project":"testone","denotations":[{"id":"T19580","span":{"begin":1318,"end":1322},"obj":"Protein"},{"id":"T7286","span":{"begin":2852,"end":2856},"obj":"Protein"},{"id":"T7285","span":{"begin":2639,"end":2643},"obj":"Protein"},{"id":"T7284","span":{"begin":2513,"end":2517},"obj":"Protein"},{"id":"T7283","span":{"begin":2472,"end":2475},"obj":"Protein"},{"id":"T7282","span":{"begin":2444,"end":2448},"obj":"Protein"},{"id":"T7281","span":{"begin":2405,"end":2408},"obj":"Protein"},{"id":"T7280","span":{"begin":2394,"end":2398},"obj":"Protein"},{"id":"T7279","span":{"begin":2355,"end":2359},"obj":"Protein"},{"id":"T7278","span":{"begin":2272,"end":2276},"obj":"Protein"},{"id":"T7277","span":{"begin":2143,"end":2147},"obj":"Protein"},{"id":"T7276","span":{"begin":2106,"end":2109},"obj":"Protein"},{"id":"T7275","span":{"begin":1981,"end":1985},"obj":"Protein"},{"id":"T7274","span":{"begin":1964,"end":1968},"obj":"Protein"},{"id":"T7273","span":{"begin":1163,"end":1167},"obj":"Protein"},{"id":"T7272","span":{"begin":960,"end":964},"obj":"Protein"},{"id":"T7271","span":{"begin":921,"end":925},"obj":"Protein"},{"id":"T7270","span":{"begin":728,"end":732},"obj":"Protein"},{"id":"T7269","span":{"begin":711,"end":715},"obj":"Protein"},{"id":"T7268","span":{"begin":364,"end":368},"obj":"Protein"},{"id":"T7267","span":{"begin":145,"end":149},"obj":"Protein"},{"id":"T7266","span":{"begin":75,"end":79},"obj":"Protein"}],"text":"Induction of CD8 T cells and NK Cell Infiltration into Tumor and Spleen of CCR5−/− Mice\nTo investigate whether the inhibition of tumor growth in CCR5−/− mice is related to tumor-specific immune responses, we analyzed the distribution patterns of CD8+ cytotoxic T cell and CD57+ Natural Killer cells in tumor and spleen tissues. By staining the tumor sections from CCR5−/− mice, we found that there was a significant influx of CD8+ cells into the tumor, as well as an increase in the number of infiltrating NK cells (Figure 5A). CD8+ T cells and CD57+ NK cells were spread diffusely throughout the entire sections. To further investigate the differences in the numbers of CD8+ T cells and CD57+ NK cells between CCR5+/+ mice and CCR5−/− mice in immunity-related organ, we also analyzed the CD8 and CD57 reactive cell number in spleen tissues. The number of CD8+ T cells and CD57+ NK cells were higher in the spleen of the CCR5−/− mice than in the spleen of the CCR5+/+ mice (Figure 5B). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in an anti-tumor effect in CCR5−/− mice.\n10.1371/journal.pone.0033747.g005 Figure 5 Induction of the infiltration of CD8+ T cells and NK cells into tumor, and increase in spleen of CCR5−/− mice.\nA and B, Immunolfluorescence analysis was used to determine the expression levels of CD8 (CD8+ cytotoxic T-cell surface marker) and CD57 (NK cell marker) in tumor and spleen sections. The images shown are representative of three separate experiments performed in triplicate. Scale bars indicate 50 µm (A) and 100 µm (B). C and D, Analysis of lymphocyte phenotypes. The tumor and spleen tissues were separated at study termination (Day 31). Flow cytometry analysis was performed using FACSAria flow cytometry, and represent data were shown. Data are means ± S.D. of four experimental animals. To analyze the cell phenotype change in CCR5−/− mice and CCR5+/+ mice by inoculation of the melanoma cell, lymphocytes were isolated from the tumor and spleen tissues. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of CCR5−/− mice tumor tissue were 7.2%, 48.2%, 16.9%, 32.1% and 7.8%, respectively, compared to 2.9%, 11.1%, 2.3%, 0.6% and 3.1% of CCR5+/+ mice (Figure 5C). The lymphocytes that infiltrated the tumor tissue of the CCR5−/− mice also had higher levels of CD19, CD3, CD4, CD8 and CD57 when compared to the CCR5+/+ mice. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of the CCR5−/− mice spleen were 61.3%, 33.4%, 17.6%, 9.2% and 0.6%, respectively compared to 38.3%, 5.9%, 4.0%, 1.0% and 3.9% of the CCR5+/+ mice (Figure 5D). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in the inhibition of tumor growth in CCR5−/− mice."}

{"project":"BioNLP16_Messiy","denotations":[{"id":"T19741","span":{"begin":1318,"end":1322},"obj":"Protein"},{"id":"T8031","span":{"begin":2852,"end":2856},"obj":"Protein"},{"id":"T8030","span":{"begin":2639,"end":2643},"obj":"Protein"},{"id":"T8029","span":{"begin":2513,"end":2517},"obj":"Protein"},{"id":"T8028","span":{"begin":2472,"end":2475},"obj":"Protein"},{"id":"T8027","span":{"begin":2444,"end":2448},"obj":"Protein"},{"id":"T8026","span":{"begin":2405,"end":2408},"obj":"Protein"},{"id":"T8025","span":{"begin":2394,"end":2398},"obj":"Protein"},{"id":"T8024","span":{"begin":2355,"end":2359},"obj":"Protein"},{"id":"T8023","span":{"begin":2272,"end":2276},"obj":"Protein"},{"id":"T8022","span":{"begin":2143,"end":2147},"obj":"Protein"},{"id":"T8021","span":{"begin":2106,"end":2109},"obj":"Protein"},{"id":"T8020","span":{"begin":1964,"end":1968},"obj":"Protein"},{"id":"T8019","span":{"begin":1981,"end":1985},"obj":"Protein"},{"id":"T8018","span":{"begin":1163,"end":1167},"obj":"Protein"},{"id":"T8017","span":{"begin":960,"end":964},"obj":"Protein"},{"id":"T8016","span":{"begin":921,"end":925},"obj":"Protein"},{"id":"T8015","span":{"begin":728,"end":732},"obj":"Protein"},{"id":"T8014","span":{"begin":711,"end":715},"obj":"Protein"},{"id":"T8013","span":{"begin":364,"end":368},"obj":"Protein"},{"id":"T8012","span":{"begin":145,"end":149},"obj":"Protein"},{"id":"T8011","span":{"begin":75,"end":79},"obj":"Protein"}],"text":"Induction of CD8 T cells and NK Cell Infiltration into Tumor and Spleen of CCR5−/− Mice\nTo investigate whether the inhibition of tumor growth in CCR5−/− mice is related to tumor-specific immune responses, we analyzed the distribution patterns of CD8+ cytotoxic T cell and CD57+ Natural Killer cells in tumor and spleen tissues. By staining the tumor sections from CCR5−/− mice, we found that there was a significant influx of CD8+ cells into the tumor, as well as an increase in the number of infiltrating NK cells (Figure 5A). CD8+ T cells and CD57+ NK cells were spread diffusely throughout the entire sections. To further investigate the differences in the numbers of CD8+ T cells and CD57+ NK cells between CCR5+/+ mice and CCR5−/− mice in immunity-related organ, we also analyzed the CD8 and CD57 reactive cell number in spleen tissues. The number of CD8+ T cells and CD57+ NK cells were higher in the spleen of the CCR5−/− mice than in the spleen of the CCR5+/+ mice (Figure 5B). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in an anti-tumor effect in CCR5−/− mice.\n10.1371/journal.pone.0033747.g005 Figure 5 Induction of the infiltration of CD8+ T cells and NK cells into tumor, and increase in spleen of CCR5−/− mice.\nA and B, Immunolfluorescence analysis was used to determine the expression levels of CD8 (CD8+ cytotoxic T-cell surface marker) and CD57 (NK cell marker) in tumor and spleen sections. The images shown are representative of three separate experiments performed in triplicate. Scale bars indicate 50 µm (A) and 100 µm (B). C and D, Analysis of lymphocyte phenotypes. The tumor and spleen tissues were separated at study termination (Day 31). Flow cytometry analysis was performed using FACSAria flow cytometry, and represent data were shown. Data are means ± S.D. of four experimental animals. To analyze the cell phenotype change in CCR5−/− mice and CCR5+/+ mice by inoculation of the melanoma cell, lymphocytes were isolated from the tumor and spleen tissues. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of CCR5−/− mice tumor tissue were 7.2%, 48.2%, 16.9%, 32.1% and 7.8%, respectively, compared to 2.9%, 11.1%, 2.3%, 0.6% and 3.1% of CCR5+/+ mice (Figure 5C). The lymphocytes that infiltrated the tumor tissue of the CCR5−/− mice also had higher levels of CD19, CD3, CD4, CD8 and CD57 when compared to the CCR5+/+ mice. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of the CCR5−/− mice spleen were 61.3%, 33.4%, 17.6%, 9.2% and 0.6%, respectively compared to 38.3%, 5.9%, 4.0%, 1.0% and 3.9% of the CCR5+/+ mice (Figure 5D). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in the inhibition of tumor growth in CCR5−/− mice."}

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of CD8 T cells and NK Cell Infiltration into Tumor and Spleen of CCR5−/− Mice\nTo investigate whether the inhibition of tumor growth in CCR5−/− mice is related to tumor-specific immune responses, we analyzed the distribution patterns of CD8+ cytotoxic T cell and CD57+ Natural Killer cells in tumor and spleen tissues. By staining the tumor sections from CCR5−/− mice, we found that there was a significant influx of CD8+ cells into the tumor, as well as an increase in the number of infiltrating NK cells (Figure 5A). CD8+ T cells and CD57+ NK cells were spread diffusely throughout the entire sections. To further investigate the differences in the numbers of CD8+ T cells and CD57+ NK cells between CCR5+/+ mice and CCR5−/− mice in immunity-related organ, we also analyzed the CD8 and CD57 reactive cell number in spleen tissues. The number of CD8+ T cells and CD57+ NK cells were higher in the spleen of the CCR5−/− mice than in the spleen of the CCR5+/+ mice (Figure 5B). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in an anti-tumor effect in CCR5−/− mice.\n10.1371/journal.pone.0033747.g005 Figure 5 Induction of the infiltration of CD8+ T cells and NK cells into tumor, and increase in spleen of CCR5−/− mice.\nA and B, Immunolfluorescence analysis was used to determine the expression levels of CD8 (CD8+ cytotoxic T-cell surface marker) and CD57 (NK cell marker) in tumor and spleen sections. The images shown are representative of three separate experiments performed in triplicate. Scale bars indicate 50 µm (A) and 100 µm (B). C and D, Analysis of lymphocyte phenotypes. The tumor and spleen tissues were separated at study termination (Day 31). Flow cytometry analysis was performed using FACSAria flow cytometry, and represent data were shown. Data are means ± S.D. of four experimental animals. To analyze the cell phenotype change in CCR5−/− mice and CCR5+/+ mice by inoculation of the melanoma cell, lymphocytes were isolated from the tumor and spleen tissues. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of CCR5−/− mice tumor tissue were 7.2%, 48.2%, 16.9%, 32.1% and 7.8%, respectively, compared to 2.9%, 11.1%, 2.3%, 0.6% and 3.1% of CCR5+/+ mice (Figure 5C). The lymphocytes that infiltrated the tumor tissue of the CCR5−/− mice also had higher levels of CD19, CD3, CD4, CD8 and CD57 when compared to the CCR5+/+ mice. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of the CCR5−/− mice spleen were 61.3%, 33.4%, 17.6%, 9.2% and 0.6%, respectively compared to 38.3%, 5.9%, 4.0%, 1.0% and 3.9% of the CCR5+/+ mice (Figure 5D). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in the inhibition of tumor growth in CCR5−/− mice."}

{"project":"bionlp-st-ge-2016-test-proteins","denotations":[{"id":"T19596","span":{"begin":1318,"end":1322},"obj":"Protein"},{"id":"T7395","span":{"begin":2852,"end":2856},"obj":"Protein"},{"id":"T7394","span":{"begin":2639,"end":2643},"obj":"Protein"},{"id":"T7393","span":{"begin":2513,"end":2517},"obj":"Protein"},{"id":"T7392","span":{"begin":2472,"end":2475},"obj":"Protein"},{"id":"T7391","span":{"begin":2444,"end":2448},"obj":"Protein"},{"id":"T7390","span":{"begin":2405,"end":2408},"obj":"Protein"},{"id":"T7389","span":{"begin":2394,"end":2398},"obj":"Protein"},{"id":"T7388","span":{"begin":2355,"end":2359},"obj":"Protein"},{"id":"T7387","span":{"begin":2272,"end":2276},"obj":"Protein"},{"id":"T7386","span":{"begin":2143,"end":2147},"obj":"Protein"},{"id":"T7385","span":{"begin":2106,"end":2109},"obj":"Protein"},{"id":"T7384","span":{"begin":1981,"end":1985},"obj":"Protein"},{"id":"T7383","span":{"begin":1964,"end":1968},"obj":"Protein"},{"id":"T7382","span":{"begin":1163,"end":1167},"obj":"Protein"},{"id":"T7381","span":{"begin":960,"end":964},"obj":"Protein"},{"id":"T7380","span":{"begin":921,"end":925},"obj":"Protein"},{"id":"T7379","span":{"begin":728,"end":732},"obj":"Protein"},{"id":"T7378","span":{"begin":711,"end":715},"obj":"Protein"},{"id":"T7377","span":{"begin":364,"end":368},"obj":"Protein"},{"id":"T7376","span":{"begin":145,"end":149},"obj":"Protein"},{"id":"T7375","span":{"begin":75,"end":79},"obj":"Protein"}],"namespaces":[{"prefix":"_base","uri":"http://bionlp.dbcls.jp/ontology/ge.owl#"}],"text":"Induction of CD8 T cells and NK Cell Infiltration into Tumor and Spleen of CCR5−/− Mice\nTo investigate whether the inhibition of tumor growth in CCR5−/− mice is related to tumor-specific immune responses, we analyzed the distribution patterns of CD8+ cytotoxic T cell and CD57+ Natural Killer cells in tumor and spleen tissues. By staining the tumor sections from CCR5−/− mice, we found that there was a significant influx of CD8+ cells into the tumor, as well as an increase in the number of infiltrating NK cells (Figure 5A). CD8+ T cells and CD57+ NK cells were spread diffusely throughout the entire sections. To further investigate the differences in the numbers of CD8+ T cells and CD57+ NK cells between CCR5+/+ mice and CCR5−/− mice in immunity-related organ, we also analyzed the CD8 and CD57 reactive cell number in spleen tissues. The number of CD8+ T cells and CD57+ NK cells were higher in the spleen of the CCR5−/− mice than in the spleen of the CCR5+/+ mice (Figure 5B). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in an anti-tumor effect in CCR5−/− mice.\n10.1371/journal.pone.0033747.g005 Figure 5 Induction of the infiltration of CD8+ T cells and NK cells into tumor, and increase in spleen of CCR5−/− mice.\nA and B, Immunolfluorescence analysis was used to determine the expression levels of CD8 (CD8+ cytotoxic T-cell surface marker) and CD57 (NK cell marker) in tumor and spleen sections. The images shown are representative of three separate experiments performed in triplicate. Scale bars indicate 50 µm (A) and 100 µm (B). C and D, Analysis of lymphocyte phenotypes. The tumor and spleen tissues were separated at study termination (Day 31). Flow cytometry analysis was performed using FACSAria flow cytometry, and represent data were shown. Data are means ± S.D. of four experimental animals. To analyze the cell phenotype change in CCR5−/− mice and CCR5+/+ mice by inoculation of the melanoma cell, lymphocytes were isolated from the tumor and spleen tissues. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of CCR5−/− mice tumor tissue were 7.2%, 48.2%, 16.9%, 32.1% and 7.8%, respectively, compared to 2.9%, 11.1%, 2.3%, 0.6% and 3.1% of CCR5+/+ mice (Figure 5C). The lymphocytes that infiltrated the tumor tissue of the CCR5−/− mice also had higher levels of CD19, CD3, CD4, CD8 and CD57 when compared to the CCR5+/+ mice. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of the CCR5−/− mice spleen were 61.3%, 33.4%, 17.6%, 9.2% and 0.6%, respectively compared to 38.3%, 5.9%, 4.0%, 1.0% and 3.9% of the CCR5+/+ mice (Figure 5D). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in the inhibition of tumor growth in CCR5−/− mice."}

{"project":"bionlp-st-ge-2016-uniprot","denotations":[{"id":"T7964","span":{"begin":2394,"end":2398},"obj":"http://www.uniprot.org/uniprot/P15391"},{"id":"T7963","span":{"begin":2264,"end":2267},"obj":"http://www.uniprot.org/uniprot/Q8IX06"},{"id":"T7962","span":{"begin":2264,"end":2267},"obj":"http://www.uniprot.org/uniprot/Q5D1E8"},{"id":"T7961","span":{"begin":2264,"end":2267},"obj":"http://www.uniprot.org/uniprot/Q5D1E7"},{"id":"T7960","span":{"begin":2472,"end":2475},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T7959","span":{"begin":2405,"end":2408},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T7958","span":{"begin":2106,"end":2109},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T7957","span":{"begin":2465,"end":2468},"obj":"http://www.uniprot.org/uniprot/P09693"},{"id":"T7956","span":{"begin":2400,"end":2403},"obj":"http://www.uniprot.org/uniprot/P09693"},{"id":"T7955","span":{"begin":2099,"end":2102},"obj":"http://www.uniprot.org/uniprot/P09693"},{"id":"T7954","span":{"begin":2465,"end":2468},"obj":"http://www.uniprot.org/uniprot/P07766"},{"id":"T7953","span":{"begin":2400,"end":2403},"obj":"http://www.uniprot.org/uniprot/P07766"},{"id":"T7952","span":{"begin":2099,"end":2102},"obj":"http://www.uniprot.org/uniprot/P07766"},{"id":"T7951","span":{"begin":2465,"end":2468},"obj":"http://www.uniprot.org/uniprot/P04234"},{"id":"T7950","span":{"begin":2400,"end":2403},"obj":"http://www.uniprot.org/uniprot/P04234"},{"id":"T7949","span":{"begin":2099,"end":2102},"obj":"http://www.uniprot.org/uniprot/P04234"},{"id":"T7948","span":{"begin":2465,"end":2468},"obj":"http://www.uniprot.org/uniprot/P20963"},{"id":"T7947","span":{"begin":2400,"end":2403},"obj":"http://www.uniprot.org/uniprot/P20963"},{"id":"T7946","span":{"begin":2099,"end":2102},"obj":"http://www.uniprot.org/uniprot/P20963"},{"id":"T7945","span":{"begin":2852,"end":2856},"obj":"http://www.uniprot.org/uniprot/P51681"},{"id":"T7944","span":{"begin":2639,"end":2643},"obj":"http://www.uniprot.org/uniprot/P51681"},{"id":"T7943","span":{"begin":2513,"end":2517},"obj":"http://www.uniprot.org/uniprot/P51681"},{"id":"T7942","span":{"begin":2444,"end":2448},"obj":"http://www.uniprot.org/uniprot/P51681"},{"id":"T7941","span":{"begin":2355,"end":2359},"obj":"http://www.uniprot.org/uniprot/P51681"},{"id":"T7940","span":{"begin":2272,"end":2276},"obj":"http://www.uniprot.org/uniprot/P51681"},{"id":"T7939","span":{"begin":2143,"end":2147},"obj":"http://www.uniprot.org/uniprot/P51681"},{"id":"T7938","span":{"begin":1981,"end":1985},"obj":"http://www.uniprot.org/uniprot/P51681"},{"id":"T7937","span":{"begin":1964,"end":1968},"obj":"http://www.uniprot.org/uniprot/P51681"},{"id":"T7936","span":{"begin":1163,"end":1167},"obj":"http://www.uniprot.org/uniprot/P51681"},{"id":"T7935","span":{"begin":960,"end":964},"obj":"http://www.uniprot.org/uniprot/P51681"},{"id":"T7934","span":{"begin":921,"end":925},"obj":"http://www.uniprot.org/uniprot/P51681"},{"id":"T7933","span":{"begin":728,"end":732},"obj":"http://www.uniprot.org/uniprot/P51681"},{"id":"T7932","span":{"begin":711,"end":715},"obj":"http://www.uniprot.org/uniprot/P51681"},{"id":"T7931","span":{"begin":364,"end":368},"obj":"http://www.uniprot.org/uniprot/P51681"},{"id":"T7930","span":{"begin":145,"end":149},"obj":"http://www.uniprot.org/uniprot/P51681"},{"id":"T7929","span":{"begin":75,"end":79},"obj":"http://www.uniprot.org/uniprot/P51681"},{"id":"T7928","span":{"begin":2722,"end":2725},"obj":"http://www.uniprot.org/uniprot/P10966"},{"id":"T7927","span":{"begin":2410,"end":2413},"obj":"http://www.uniprot.org/uniprot/P10966"},{"id":"T7926","span":{"begin":1043,"end":1046},"obj":"http://www.uniprot.org/uniprot/P10966"},{"id":"T7925","span":{"begin":856,"end":859},"obj":"http://www.uniprot.org/uniprot/P10966"},{"id":"T7924","span":{"begin":789,"end":792},"obj":"http://www.uniprot.org/uniprot/P10966"},{"id":"T7923","span":{"begin":671,"end":674},"obj":"http://www.uniprot.org/uniprot/P10966"},{"id":"T7922","span":{"begin":528,"end":531},"obj":"http://www.uniprot.org/uniprot/P10966"},{"id":"T7921","span":{"begin":426,"end":429},"obj":"http://www.uniprot.org/uniprot/P10966"},{"id":"T7920","span":{"begin":246,"end":249},"obj":"http://www.uniprot.org/uniprot/P10966"},{"id":"T7919","span":{"begin":13,"end":16},"obj":"http://www.uniprot.org/uniprot/P10966"},{"id":"T7918","span":{"begin":2722,"end":2725},"obj":"http://www.uniprot.org/uniprot/P01732"},{"id":"T7917","span":{"begin":2410,"end":2413},"obj":"http://www.uniprot.org/uniprot/P01732"},{"id":"T7916","span":{"begin":1043,"end":1046},"obj":"http://www.uniprot.org/uniprot/P01732"},{"id":"T7915","span":{"begin":856,"end":859},"obj":"http://www.uniprot.org/uniprot/P01732"},{"id":"T7914","span":{"begin":789,"end":792},"obj":"http://www.uniprot.org/uniprot/P01732"},{"id":"T7913","span":{"begin":671,"end":674},"obj":"http://www.uniprot.org/uniprot/P01732"},{"id":"T7912","span":{"begin":528,"end":531},"obj":"http://www.uniprot.org/uniprot/P01732"},{"id":"T7911","span":{"begin":426,"end":429},"obj":"http://www.uniprot.org/uniprot/P01732"},{"id":"T7910","span":{"begin":246,"end":249},"obj":"http://www.uniprot.org/uniprot/P01732"},{"id":"T7909","span":{"begin":13,"end":16},"obj":"http://www.uniprot.org/uniprot/P01732"},{"id":"T19738","span":{"begin":1318,"end":1322},"obj":"http://www.uniprot.org/uniprot/P51681"},{"id":"T19737","span":{"begin":1422,"end":1425},"obj":"http://www.uniprot.org/uniprot/P10966"},{"id":"T19736","span":{"begin":1417,"end":1420},"obj":"http://www.uniprot.org/uniprot/P10966"},{"id":"T19735","span":{"begin":1254,"end":1257},"obj":"http://www.uniprot.org/uniprot/P10966"},{"id":"T19734","span":{"begin":1422,"end":1425},"obj":"http://www.uniprot.org/uniprot/P01732"},{"id":"T19733","span":{"begin":1417,"end":1420},"obj":"http://www.uniprot.org/uniprot/P01732"},{"id":"T19732","span":{"begin":1254,"end":1257},"obj":"http://www.uniprot.org/uniprot/P01732"}],"namespaces":[{"prefix":"_base","uri":"http://www.uniprot.org/uniprot/"}],"text":"Induction of CD8 T cells and NK Cell Infiltration into Tumor and Spleen of CCR5−/− Mice\nTo investigate whether the inhibition of tumor growth in CCR5−/− mice is related to tumor-specific immune responses, we analyzed the distribution patterns of CD8+ cytotoxic T cell and CD57+ Natural Killer cells in tumor and spleen tissues. By staining the tumor sections from CCR5−/− mice, we found that there was a significant influx of CD8+ cells into the tumor, as well as an increase in the number of infiltrating NK cells (Figure 5A). CD8+ T cells and CD57+ NK cells were spread diffusely throughout the entire sections. To further investigate the differences in the numbers of CD8+ T cells and CD57+ NK cells between CCR5+/+ mice and CCR5−/− mice in immunity-related organ, we also analyzed the CD8 and CD57 reactive cell number in spleen tissues. The number of CD8+ T cells and CD57+ NK cells were higher in the spleen of the CCR5−/− mice than in the spleen of the CCR5+/+ mice (Figure 5B). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in an anti-tumor effect in CCR5−/− mice.\n10.1371/journal.pone.0033747.g005 Figure 5 Induction of the infiltration of CD8+ T cells and NK cells into tumor, and increase in spleen of CCR5−/− mice.\nA and B, Immunolfluorescence analysis was used to determine the expression levels of CD8 (CD8+ cytotoxic T-cell surface marker) and CD57 (NK cell marker) in tumor and spleen sections. The images shown are representative of three separate experiments performed in triplicate. Scale bars indicate 50 µm (A) and 100 µm (B). C and D, Analysis of lymphocyte phenotypes. The tumor and spleen tissues were separated at study termination (Day 31). Flow cytometry analysis was performed using FACSAria flow cytometry, and represent data were shown. Data are means ± S.D. of four experimental animals. To analyze the cell phenotype change in CCR5−/− mice and CCR5+/+ mice by inoculation of the melanoma cell, lymphocytes were isolated from the tumor and spleen tissues. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of CCR5−/− mice tumor tissue were 7.2%, 48.2%, 16.9%, 32.1% and 7.8%, respectively, compared to 2.9%, 11.1%, 2.3%, 0.6% and 3.1% of CCR5+/+ mice (Figure 5C). The lymphocytes that infiltrated the tumor tissue of the CCR5−/− mice also had higher levels of CD19, CD3, CD4, CD8 and CD57 when compared to the CCR5+/+ mice. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of the CCR5−/− mice spleen were 61.3%, 33.4%, 17.6%, 9.2% and 0.6%, respectively compared to 38.3%, 5.9%, 4.0%, 1.0% and 3.9% of the CCR5+/+ mice (Figure 5D). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in the inhibition of tumor growth in CCR5−/− mice."}

{"project":"UBERON-AE","denotations":[{"id":"T19586","span":{"begin":1718,"end":1725},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"T19585","span":{"begin":1711,"end":1717},"obj":"http://purl.obolibrary.org/obo/UBERON_0002106"},{"id":"T19584","span":{"begin":1499,"end":1505},"obj":"http://purl.obolibrary.org/obo/UBERON_0002106"},{"id":"T19583","span":{"begin":1308,"end":1314},"obj":"http://purl.obolibrary.org/obo/UBERON_0002106"},{"id":"T7341","span":{"begin":761,"end":766},"obj":"http://purl.obolibrary.org/obo/UBERON_0000062"},{"id":"T7340","span":{"begin":2341,"end":2347},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"T7339","span":{"begin":2162,"end":2168},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"T7338","span":{"begin":2083,"end":2090},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"T7337","span":{"begin":833,"end":840},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"T7336","span":{"begin":319,"end":326},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"T7335","span":{"begin":2526,"end":2532},"obj":"http://purl.obolibrary.org/obo/UBERON_0002106"},{"id":"T7334","span":{"begin":2076,"end":2082},"obj":"http://purl.obolibrary.org/obo/UBERON_0002106"},{"id":"T7333","span":{"begin":946,"end":952},"obj":"http://purl.obolibrary.org/obo/UBERON_0002106"},{"id":"T7332","span":{"begin":907,"end":913},"obj":"http://purl.obolibrary.org/obo/UBERON_0002106"},{"id":"T7331","span":{"begin":826,"end":832},"obj":"http://purl.obolibrary.org/obo/UBERON_0002106"},{"id":"T7330","span":{"begin":312,"end":318},"obj":"http://purl.obolibrary.org/obo/UBERON_0002106"},{"id":"T7329","span":{"begin":65,"end":71},"obj":"http://purl.obolibrary.org/obo/UBERON_0002106"}],"text":"Induction of CD8 T cells and NK Cell Infiltration into Tumor and Spleen of CCR5−/− Mice\nTo investigate whether the inhibition of tumor growth in CCR5−/− mice is related to tumor-specific immune responses, we analyzed the distribution patterns of CD8+ cytotoxic T cell and CD57+ Natural Killer cells in tumor and spleen tissues. By staining the tumor sections from CCR5−/− mice, we found that there was a significant influx of CD8+ cells into the tumor, as well as an increase in the number of infiltrating NK cells (Figure 5A). CD8+ T cells and CD57+ NK cells were spread diffusely throughout the entire sections. To further investigate the differences in the numbers of CD8+ T cells and CD57+ NK cells between CCR5+/+ mice and CCR5−/− mice in immunity-related organ, we also analyzed the CD8 and CD57 reactive cell number in spleen tissues. The number of CD8+ T cells and CD57+ NK cells were higher in the spleen of the CCR5−/− mice than in the spleen of the CCR5+/+ mice (Figure 5B). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in an anti-tumor effect in CCR5−/− mice.\n10.1371/journal.pone.0033747.g005 Figure 5 Induction of the infiltration of CD8+ T cells and NK cells into tumor, and increase in spleen of CCR5−/− mice.\nA and B, Immunolfluorescence analysis was used to determine the expression levels of CD8 (CD8+ cytotoxic T-cell surface marker) and CD57 (NK cell marker) in tumor and spleen sections. The images shown are representative of three separate experiments performed in triplicate. Scale bars indicate 50 µm (A) and 100 µm (B). C and D, Analysis of lymphocyte phenotypes. The tumor and spleen tissues were separated at study termination (Day 31). Flow cytometry analysis was performed using FACSAria flow cytometry, and represent data were shown. Data are means ± S.D. of four experimental animals. To analyze the cell phenotype change in CCR5−/− mice and CCR5+/+ mice by inoculation of the melanoma cell, lymphocytes were isolated from the tumor and spleen tissues. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of CCR5−/− mice tumor tissue were 7.2%, 48.2%, 16.9%, 32.1% and 7.8%, respectively, compared to 2.9%, 11.1%, 2.3%, 0.6% and 3.1% of CCR5+/+ mice (Figure 5C). The lymphocytes that infiltrated the tumor tissue of the CCR5−/− mice also had higher levels of CD19, CD3, CD4, CD8 and CD57 when compared to the CCR5+/+ mice. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of the CCR5−/− mice spleen were 61.3%, 33.4%, 17.6%, 9.2% and 0.6%, respectively compared to 38.3%, 5.9%, 4.0%, 1.0% and 3.9% of the CCR5+/+ mice (Figure 5D). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in the inhibition of tumor growth in CCR5−/− mice."}

{"project":"GO-BP","denotations":[{"id":"T7398","span":{"begin":187,"end":203},"obj":"http://purl.obolibrary.org/obo/GO_0006955"},{"id":"T7397","span":{"begin":2842,"end":2848},"obj":"http://purl.obolibrary.org/obo/GO_0040007"},{"id":"T7396","span":{"begin":135,"end":141},"obj":"http://purl.obolibrary.org/obo/GO_0040007"}],"text":"Induction of CD8 T cells and NK Cell Infiltration into Tumor and Spleen of CCR5−/− Mice\nTo investigate whether the inhibition of tumor growth in CCR5−/− mice is related to tumor-specific immune responses, we analyzed the distribution patterns of CD8+ cytotoxic T cell and CD57+ Natural Killer cells in tumor and spleen tissues. By staining the tumor sections from CCR5−/− mice, we found that there was a significant influx of CD8+ cells into the tumor, as well as an increase in the number of infiltrating NK cells (Figure 5A). CD8+ T cells and CD57+ NK cells were spread diffusely throughout the entire sections. To further investigate the differences in the numbers of CD8+ T cells and CD57+ NK cells between CCR5+/+ mice and CCR5−/− mice in immunity-related organ, we also analyzed the CD8 and CD57 reactive cell number in spleen tissues. The number of CD8+ T cells and CD57+ NK cells were higher in the spleen of the CCR5−/− mice than in the spleen of the CCR5+/+ mice (Figure 5B). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in an anti-tumor effect in CCR5−/− mice.\n10.1371/journal.pone.0033747.g005 Figure 5 Induction of the infiltration of CD8+ T cells and NK cells into tumor, and increase in spleen of CCR5−/− mice.\nA and B, Immunolfluorescence analysis was used to determine the expression levels of CD8 (CD8+ cytotoxic T-cell surface marker) and CD57 (NK cell marker) in tumor and spleen sections. The images shown are representative of three separate experiments performed in triplicate. Scale bars indicate 50 µm (A) and 100 µm (B). C and D, Analysis of lymphocyte phenotypes. The tumor and spleen tissues were separated at study termination (Day 31). Flow cytometry analysis was performed using FACSAria flow cytometry, and represent data were shown. Data are means ± S.D. of four experimental animals. To analyze the cell phenotype change in CCR5−/− mice and CCR5+/+ mice by inoculation of the melanoma cell, lymphocytes were isolated from the tumor and spleen tissues. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of CCR5−/− mice tumor tissue were 7.2%, 48.2%, 16.9%, 32.1% and 7.8%, respectively, compared to 2.9%, 11.1%, 2.3%, 0.6% and 3.1% of CCR5+/+ mice (Figure 5C). The lymphocytes that infiltrated the tumor tissue of the CCR5−/− mice also had higher levels of CD19, CD3, CD4, CD8 and CD57 when compared to the CCR5+/+ mice. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of the CCR5−/− mice spleen were 61.3%, 33.4%, 17.6%, 9.2% and 0.6%, respectively compared to 38.3%, 5.9%, 4.0%, 1.0% and 3.9% of the CCR5+/+ mice (Figure 5D). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in the inhibition of tumor growth in CCR5−/− mice."}

{"project":"GO-CC","denotations":[{"id":"T19601","span":{"begin":1439,"end":1451},"obj":"http://purl.obolibrary.org/obo/GO_0009986"},{"id":"T19600","span":{"begin":1473,"end":1477},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T19599","span":{"begin":1439,"end":1443},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T19598","span":{"begin":1274,"end":1279},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T19597","span":{"begin":1261,"end":1266},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T7412","span":{"begin":2741,"end":2746},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T7411","span":{"begin":2728,"end":2733},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T7410","span":{"begin":1062,"end":1067},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T7409","span":{"begin":1049,"end":1054},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T7408","span":{"begin":882,"end":887},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T7407","span":{"begin":863,"end":868},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T7406","span":{"begin":697,"end":702},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T7405","span":{"begin":678,"end":683},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T7404","span":{"begin":554,"end":559},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T7403","span":{"begin":535,"end":540},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T7402","span":{"begin":509,"end":514},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T7401","span":{"begin":431,"end":436},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T7400","span":{"begin":293,"end":298},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T7399","span":{"begin":19,"end":24},"obj":"http://purl.obolibrary.org/obo/GO_0005623"}],"text":"Induction of CD8 T cells and NK Cell Infiltration into Tumor and Spleen of CCR5−/− Mice\nTo investigate whether the inhibition of tumor growth in CCR5−/− mice is related to tumor-specific immune responses, we analyzed the distribution patterns of CD8+ cytotoxic T cell and CD57+ Natural Killer cells in tumor and spleen tissues. By staining the tumor sections from CCR5−/− mice, we found that there was a significant influx of CD8+ cells into the tumor, as well as an increase in the number of infiltrating NK cells (Figure 5A). CD8+ T cells and CD57+ NK cells were spread diffusely throughout the entire sections. To further investigate the differences in the numbers of CD8+ T cells and CD57+ NK cells between CCR5+/+ mice and CCR5−/− mice in immunity-related organ, we also analyzed the CD8 and CD57 reactive cell number in spleen tissues. The number of CD8+ T cells and CD57+ NK cells were higher in the spleen of the CCR5−/− mice than in the spleen of the CCR5+/+ mice (Figure 5B). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in an anti-tumor effect in CCR5−/− mice.\n10.1371/journal.pone.0033747.g005 Figure 5 Induction of the infiltration of CD8+ T cells and NK cells into tumor, and increase in spleen of CCR5−/− mice.\nA and B, Immunolfluorescence analysis was used to determine the expression levels of CD8 (CD8+ cytotoxic T-cell surface marker) and CD57 (NK cell marker) in tumor and spleen sections. The images shown are representative of three separate experiments performed in triplicate. Scale bars indicate 50 µm (A) and 100 µm (B). C and D, Analysis of lymphocyte phenotypes. The tumor and spleen tissues were separated at study termination (Day 31). Flow cytometry analysis was performed using FACSAria flow cytometry, and represent data were shown. Data are means ± S.D. of four experimental animals. To analyze the cell phenotype change in CCR5−/− mice and CCR5+/+ mice by inoculation of the melanoma cell, lymphocytes were isolated from the tumor and spleen tissues. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of CCR5−/− mice tumor tissue were 7.2%, 48.2%, 16.9%, 32.1% and 7.8%, respectively, compared to 2.9%, 11.1%, 2.3%, 0.6% and 3.1% of CCR5+/+ mice (Figure 5C). The lymphocytes that infiltrated the tumor tissue of the CCR5−/− mice also had higher levels of CD19, CD3, CD4, CD8 and CD57 when compared to the CCR5+/+ mice. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of the CCR5−/− mice spleen were 61.3%, 33.4%, 17.6%, 9.2% and 0.6%, respectively compared to 38.3%, 5.9%, 4.0%, 1.0% and 3.9% of the CCR5+/+ mice (Figure 5D). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in the inhibition of tumor growth in CCR5−/− mice."}

{"project":"sentences","denotations":[{"id":"T19594","span":{"begin":1872,"end":1923},"obj":"Sentence"},{"id":"T19593","span":{"begin":1772,"end":1871},"obj":"Sentence"},{"id":"T19592","span":{"begin":1697,"end":1771},"obj":"Sentence"},{"id":"T19591","span":{"begin":1653,"end":1696},"obj":"Sentence"},{"id":"T19590","span":{"begin":1607,"end":1652},"obj":"Sentence"},{"id":"T19589","span":{"begin":1516,"end":1606},"obj":"Sentence"},{"id":"T19588","span":{"begin":1332,"end":1515},"obj":"Sentence"},{"id":"T19587","span":{"begin":1221,"end":1331},"obj":"Sentence"},{"id":"T7353","span":{"begin":2665,"end":2865},"obj":"Sentence"},{"id":"T7352","span":{"begin":2458,"end":2664},"obj":"Sentence"},{"id":"T7351","span":{"begin":2298,"end":2457},"obj":"Sentence"},{"id":"T7350","span":{"begin":2092,"end":2297},"obj":"Sentence"},{"id":"T7349","span":{"begin":1924,"end":2091},"obj":"Sentence"},{"id":"T7348","span":{"begin":986,"end":1176},"obj":"Sentence"},{"id":"T7347","span":{"begin":842,"end":985},"obj":"Sentence"},{"id":"T7346","span":{"begin":614,"end":841},"obj":"Sentence"},{"id":"T7345","span":{"begin":528,"end":613},"obj":"Sentence"},{"id":"T7344","span":{"begin":328,"end":527},"obj":"Sentence"},{"id":"T7343","span":{"begin":88,"end":327},"obj":"Sentence"},{"id":"T7342","span":{"begin":0,"end":87},"obj":"Sentence"},{"id":"T131","span":{"begin":0,"end":87},"obj":"Sentence"},{"id":"T132","span":{"begin":88,"end":327},"obj":"Sentence"},{"id":"T133","span":{"begin":328,"end":527},"obj":"Sentence"},{"id":"T134","span":{"begin":528,"end":613},"obj":"Sentence"},{"id":"T135","span":{"begin":614,"end":841},"obj":"Sentence"},{"id":"T136","span":{"begin":842,"end":985},"obj":"Sentence"},{"id":"T137","span":{"begin":986,"end":1176},"obj":"Sentence"},{"id":"T138","span":{"begin":1177,"end":1331},"obj":"Sentence"},{"id":"T139","span":{"begin":1332,"end":1515},"obj":"Sentence"},{"id":"T140","span":{"begin":1516,"end":1606},"obj":"Sentence"},{"id":"T141","span":{"begin":1607,"end":1652},"obj":"Sentence"},{"id":"T142","span":{"begin":1653,"end":1696},"obj":"Sentence"},{"id":"T143","span":{"begin":1697,"end":1771},"obj":"Sentence"},{"id":"T144","span":{"begin":1772,"end":1871},"obj":"Sentence"},{"id":"T145","span":{"begin":1872,"end":1923},"obj":"Sentence"},{"id":"T146","span":{"begin":1924,"end":2091},"obj":"Sentence"},{"id":"T147","span":{"begin":2092,"end":2297},"obj":"Sentence"},{"id":"T148","span":{"begin":2298,"end":2457},"obj":"Sentence"},{"id":"T149","span":{"begin":2458,"end":2664},"obj":"Sentence"},{"id":"T150","span":{"begin":2665,"end":2865},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Induction of CD8 T cells and NK Cell Infiltration into Tumor and Spleen of CCR5−/− Mice\nTo investigate whether the inhibition of tumor growth in CCR5−/− mice is related to tumor-specific immune responses, we analyzed the distribution patterns of CD8+ cytotoxic T cell and CD57+ Natural Killer cells in tumor and spleen tissues. By staining the tumor sections from CCR5−/− mice, we found that there was a significant influx of CD8+ cells into the tumor, as well as an increase in the number of infiltrating NK cells (Figure 5A). CD8+ T cells and CD57+ NK cells were spread diffusely throughout the entire sections. To further investigate the differences in the numbers of CD8+ T cells and CD57+ NK cells between CCR5+/+ mice and CCR5−/− mice in immunity-related organ, we also analyzed the CD8 and CD57 reactive cell number in spleen tissues. The number of CD8+ T cells and CD57+ NK cells were higher in the spleen of the CCR5−/− mice than in the spleen of the CCR5+/+ mice (Figure 5B). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in an anti-tumor effect in CCR5−/− mice.\n10.1371/journal.pone.0033747.g005 Figure 5 Induction of the infiltration of CD8+ T cells and NK cells into tumor, and increase in spleen of CCR5−/− mice.\nA and B, Immunolfluorescence analysis was used to determine the expression levels of CD8 (CD8+ cytotoxic T-cell surface marker) and CD57 (NK cell marker) in tumor and spleen sections. The images shown are representative of three separate experiments performed in triplicate. Scale bars indicate 50 µm (A) and 100 µm (B). C and D, Analysis of lymphocyte phenotypes. The tumor and spleen tissues were separated at study termination (Day 31). Flow cytometry analysis was performed using FACSAria flow cytometry, and represent data were shown. Data are means ± S.D. of four experimental animals. To analyze the cell phenotype change in CCR5−/− mice and CCR5+/+ mice by inoculation of the melanoma cell, lymphocytes were isolated from the tumor and spleen tissues. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of CCR5−/− mice tumor tissue were 7.2%, 48.2%, 16.9%, 32.1% and 7.8%, respectively, compared to 2.9%, 11.1%, 2.3%, 0.6% and 3.1% of CCR5+/+ mice (Figure 5C). The lymphocytes that infiltrated the tumor tissue of the CCR5−/− mice also had higher levels of CD19, CD3, CD4, CD8 and CD57 when compared to the CCR5+/+ mice. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of the CCR5−/− mice spleen were 61.3%, 33.4%, 17.6%, 9.2% and 0.6%, respectively compared to 38.3%, 5.9%, 4.0%, 1.0% and 3.9% of the CCR5+/+ mice (Figure 5D). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in the inhibition of tumor growth in CCR5−/− mice."}

{"project":"simple1","denotations":[{"id":"T19602","span":{"begin":1318,"end":1322},"obj":"Protein"},{"id":"T7433","span":{"begin":2852,"end":2856},"obj":"Protein"},{"id":"T7432","span":{"begin":2639,"end":2643},"obj":"Protein"},{"id":"T7431","span":{"begin":2513,"end":2517},"obj":"Protein"},{"id":"T7430","span":{"begin":2472,"end":2475},"obj":"Protein"},{"id":"T7429","span":{"begin":2444,"end":2448},"obj":"Protein"},{"id":"T7428","span":{"begin":2405,"end":2408},"obj":"Protein"},{"id":"T7427","span":{"begin":2394,"end":2398},"obj":"Protein"},{"id":"T7426","span":{"begin":2355,"end":2359},"obj":"Protein"},{"id":"T7425","span":{"begin":2272,"end":2276},"obj":"Protein"},{"id":"T7424","span":{"begin":2143,"end":2147},"obj":"Protein"},{"id":"T7423","span":{"begin":2106,"end":2109},"obj":"Protein"},{"id":"T7422","span":{"begin":1981,"end":1985},"obj":"Protein"},{"id":"T7421","span":{"begin":1964,"end":1968},"obj":"Protein"},{"id":"T7420","span":{"begin":1163,"end":1167},"obj":"Protein"},{"id":"T7419","span":{"begin":960,"end":964},"obj":"Protein"},{"id":"T7418","span":{"begin":921,"end":925},"obj":"Protein"},{"id":"T7417","span":{"begin":728,"end":732},"obj":"Protein"},{"id":"T7416","span":{"begin":711,"end":715},"obj":"Protein"},{"id":"T7415","span":{"begin":364,"end":368},"obj":"Protein"},{"id":"T7414","span":{"begin":145,"end":149},"obj":"Protein"},{"id":"T7413","span":{"begin":75,"end":79},"obj":"Protein"}],"text":"Induction of CD8 T cells and NK Cell Infiltration into Tumor and Spleen of CCR5−/− Mice\nTo investigate whether the inhibition of tumor growth in CCR5−/− mice is related to tumor-specific immune responses, we analyzed the distribution patterns of CD8+ cytotoxic T cell and CD57+ Natural Killer cells in tumor and spleen tissues. By staining the tumor sections from CCR5−/− mice, we found that there was a significant influx of CD8+ cells into the tumor, as well as an increase in the number of infiltrating NK cells (Figure 5A). CD8+ T cells and CD57+ NK cells were spread diffusely throughout the entire sections. To further investigate the differences in the numbers of CD8+ T cells and CD57+ NK cells between CCR5+/+ mice and CCR5−/− mice in immunity-related organ, we also analyzed the CD8 and CD57 reactive cell number in spleen tissues. The number of CD8+ T cells and CD57+ NK cells were higher in the spleen of the CCR5−/− mice than in the spleen of the CCR5+/+ mice (Figure 5B). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in an anti-tumor effect in CCR5−/− mice.\n10.1371/journal.pone.0033747.g005 Figure 5 Induction of the infiltration of CD8+ T cells and NK cells into tumor, and increase in spleen of CCR5−/− mice.\nA and B, Immunolfluorescence analysis was used to determine the expression levels of CD8 (CD8+ cytotoxic T-cell surface marker) and CD57 (NK cell marker) in tumor and spleen sections. The images shown are representative of three separate experiments performed in triplicate. Scale bars indicate 50 µm (A) and 100 µm (B). C and D, Analysis of lymphocyte phenotypes. The tumor and spleen tissues were separated at study termination (Day 31). Flow cytometry analysis was performed using FACSAria flow cytometry, and represent data were shown. Data are means ± S.D. of four experimental animals. To analyze the cell phenotype change in CCR5−/− mice and CCR5+/+ mice by inoculation of the melanoma cell, lymphocytes were isolated from the tumor and spleen tissues. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of CCR5−/− mice tumor tissue were 7.2%, 48.2%, 16.9%, 32.1% and 7.8%, respectively, compared to 2.9%, 11.1%, 2.3%, 0.6% and 3.1% of CCR5+/+ mice (Figure 5C). The lymphocytes that infiltrated the tumor tissue of the CCR5−/− mice also had higher levels of CD19, CD3, CD4, CD8 and CD57 when compared to the CCR5+/+ mice. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of the CCR5−/− mice spleen were 61.3%, 33.4%, 17.6%, 9.2% and 0.6%, respectively compared to 38.3%, 5.9%, 4.0%, 1.0% and 3.9% of the CCR5+/+ mice (Figure 5D). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in the inhibition of tumor growth in CCR5−/− mice."}

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of CD8 T cells and NK Cell Infiltration into Tumor and Spleen of CCR5−/− Mice\nTo investigate whether the inhibition of tumor growth in CCR5−/− mice is related to tumor-specific immune responses, we analyzed the distribution patterns of CD8+ cytotoxic T cell and CD57+ Natural Killer cells in tumor and spleen tissues. 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These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in an anti-tumor effect in CCR5−/− mice.\n10.1371/journal.pone.0033747.g005 Figure 5 Induction of the infiltration of CD8+ T cells and NK cells into tumor, and increase in spleen of CCR5−/− mice.\nA and B, Immunolfluorescence analysis was used to determine the expression levels of CD8 (CD8+ cytotoxic T-cell surface marker) and CD57 (NK cell marker) in tumor and spleen sections. The images shown are representative of three separate experiments performed in triplicate. Scale bars indicate 50 µm (A) and 100 µm (B). C and D, Analysis of lymphocyte phenotypes. The tumor and spleen tissues were separated at study termination (Day 31). Flow cytometry analysis was performed using FACSAria flow cytometry, and represent data were shown. Data are means ± S.D. of four experimental animals. To analyze the cell phenotype change in CCR5−/− mice and CCR5+/+ mice by inoculation of the melanoma cell, lymphocytes were isolated from the tumor and spleen tissues. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of CCR5−/− mice tumor tissue were 7.2%, 48.2%, 16.9%, 32.1% and 7.8%, respectively, compared to 2.9%, 11.1%, 2.3%, 0.6% and 3.1% of CCR5+/+ mice (Figure 5C). The lymphocytes that infiltrated the tumor tissue of the CCR5−/− mice also had higher levels of CD19, CD3, CD4, CD8 and CD57 when compared to the CCR5+/+ mice. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of the CCR5−/− mice spleen were 61.3%, 33.4%, 17.6%, 9.2% and 0.6%, respectively compared to 38.3%, 5.9%, 4.0%, 1.0% and 3.9% of the CCR5+/+ mice (Figure 5D). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in the inhibition of tumor growth in CCR5−/− mice."}

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of CD8 T cells and NK Cell Infiltration into Tumor and Spleen of CCR5−/− Mice\nTo investigate whether the inhibition of tumor growth in CCR5−/− mice is related to tumor-specific immune responses, we analyzed the distribution patterns of CD8+ cytotoxic T cell and CD57+ Natural Killer cells in tumor and spleen tissues. By staining the tumor sections from CCR5−/− mice, we found that there was a significant influx of CD8+ cells into the tumor, as well as an increase in the number of infiltrating NK cells (Figure 5A). CD8+ T cells and CD57+ NK cells were spread diffusely throughout the entire sections. To further investigate the differences in the numbers of CD8+ T cells and CD57+ NK cells between CCR5+/+ mice and CCR5−/− mice in immunity-related organ, we also analyzed the CD8 and CD57 reactive cell number in spleen tissues. The number of CD8+ T cells and CD57+ NK cells were higher in the spleen of the CCR5−/− mice than in the spleen of the CCR5+/+ mice (Figure 5B). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in an anti-tumor effect in CCR5−/− mice.\n10.1371/journal.pone.0033747.g005 Figure 5 Induction of the infiltration of CD8+ T cells and NK cells into tumor, and increase in spleen of CCR5−/− mice.\nA and B, Immunolfluorescence analysis was used to determine the expression levels of CD8 (CD8+ cytotoxic T-cell surface marker) and CD57 (NK cell marker) in tumor and spleen sections. The images shown are representative of three separate experiments performed in triplicate. Scale bars indicate 50 µm (A) and 100 µm (B). C and D, Analysis of lymphocyte phenotypes. The tumor and spleen tissues were separated at study termination (Day 31). Flow cytometry analysis was performed using FACSAria flow cytometry, and represent data were shown. Data are means ± S.D. of four experimental animals. To analyze the cell phenotype change in CCR5−/− mice and CCR5+/+ mice by inoculation of the melanoma cell, lymphocytes were isolated from the tumor and spleen tissues. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of CCR5−/− mice tumor tissue were 7.2%, 48.2%, 16.9%, 32.1% and 7.8%, respectively, compared to 2.9%, 11.1%, 2.3%, 0.6% and 3.1% of CCR5+/+ mice (Figure 5C). The lymphocytes that infiltrated the tumor tissue of the CCR5−/− mice also had higher levels of CD19, CD3, CD4, CD8 and CD57 when compared to the CCR5+/+ mice. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of the CCR5−/− mice spleen were 61.3%, 33.4%, 17.6%, 9.2% and 0.6%, respectively compared to 38.3%, 5.9%, 4.0%, 1.0% and 3.9% of the CCR5+/+ mice (Figure 5D). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in the inhibition of tumor growth in CCR5−/− mice."}

{"project":"bionlp-st-ge-2016-test-tees","denotations":[{"id":"T19747","span":{"begin":1396,"end":1406},"obj":"Gene_expression"},{"id":"T19746","span":{"begin":1396,"end":1406},"obj":"Gene_expression"},{"id":"T19745","span":{"begin":1464,"end":1468},"obj":"Protein"},{"id":"T19744","span":{"begin":1422,"end":1425},"obj":"Protein"},{"id":"T19743","span":{"begin":1417,"end":1420},"obj":"Protein"},{"id":"T19742","span":{"begin":1254,"end":1258},"obj":"Protein"},{"id":"T8066","span":{"begin":2722,"end":2727},"obj":"Protein"},{"id":"T8065","span":{"begin":2639,"end":2643},"obj":"Protein"},{"id":"T8064","span":{"begin":2479,"end":2483},"obj":"Protein"},{"id":"T8063","span":{"begin":2472,"end":2477},"obj":"Protein"},{"id":"T8062","span":{"begin":2465,"end":2470},"obj":"Protein"},{"id":"T8061","span":{"begin":2384,"end":2390},"obj":"Gene_expression"},{"id":"T8060","span":{"begin":2384,"end":2390},"obj":"Gene_expression"},{"id":"T8059","span":{"begin":2384,"end":2390},"obj":"Gene_expression"},{"id":"T8058","span":{"begin":2384,"end":2390},"obj":"Gene_expression"},{"id":"T8057","span":{"begin":2384,"end":2390},"obj":"Gene_expression"},{"id":"T8056","span":{"begin":2418,"end":2422},"obj":"Protein"},{"id":"T8055","span":{"begin":2410,"end":2413},"obj":"Protein"},{"id":"T8054","span":{"begin":2405,"end":2408},"obj":"Protein"},{"id":"T8053","span":{"begin":2400,"end":2403},"obj":"Protein"},{"id":"T8052","span":{"begin":2394,"end":2398},"obj":"Protein"},{"id":"T8051","span":{"begin":2143,"end":2147},"obj":"Protein"},{"id":"T8050","span":{"begin":2113,"end":2117},"obj":"Protein"},{"id":"T8049","span":{"begin":2106,"end":2111},"obj":"Protein"},{"id":"T8048","span":{"begin":2099,"end":2104},"obj":"Protein"},{"id":"T8047","span":{"begin":1043,"end":1048},"obj":"Protein"},{"id":"T8046","span":{"begin":960,"end":964},"obj":"Protein"},{"id":"T8045","span":{"begin":873,"end":878},"obj":"Protein"},{"id":"T8044","span":{"begin":856,"end":860},"obj":"Protein"},{"id":"T8043","span":{"begin":797,"end":801},"obj":"Protein"},{"id":"T8042","span":{"begin":789,"end":792},"obj":"Protein"},{"id":"T8041","span":{"begin":711,"end":715},"obj":"Protein"},{"id":"T8040","span":{"begin":688,"end":693},"obj":"Protein"},{"id":"T8039","span":{"begin":671,"end":675},"obj":"Protein"},{"id":"T8038","span":{"begin":545,"end":550},"obj":"Protein"},{"id":"T8037","span":{"begin":528,"end":532},"obj":"Protein"},{"id":"T8036","span":{"begin":426,"end":430},"obj":"Protein"},{"id":"T8035","span":{"begin":272,"end":277},"obj":"Protein"},{"id":"T8034","span":{"begin":246,"end":249},"obj":"Protein"},{"id":"T8033","span":{"begin":0,"end":9},"obj":"Positive_regulation"},{"id":"T8032","span":{"begin":13,"end":18},"obj":"Protein"}],"relations":[{"id":"R5355","pred":"themeOf","subj":"T8032","obj":"T8033"},{"id":"R5356","pred":"themeOf","subj":"T8052","obj":"T8057"},{"id":"R5357","pred":"themeOf","subj":"T8053","obj":"T8058"},{"id":"R5358","pred":"themeOf","subj":"T8054","obj":"T8059"},{"id":"R5359","pred":"themeOf","subj":"T8055","obj":"T8060"},{"id":"R5360","pred":"themeOf","subj":"T8056","obj":"T8061"},{"id":"R14199","pred":"themeOf","subj":"T19743","obj":"T19746"},{"id":"R14200","pred":"themeOf","subj":"T19745","obj":"T19747"}],"text":"Induction of CD8 T cells and NK Cell Infiltration into Tumor and Spleen of CCR5−/− Mice\nTo investigate whether the inhibition of tumor growth in CCR5−/− mice is related to tumor-specific immune responses, we analyzed the distribution patterns of CD8+ cytotoxic T cell and CD57+ Natural Killer cells in tumor and spleen tissues. By staining the tumor sections from CCR5−/− mice, we found that there was a significant influx of CD8+ cells into the tumor, as well as an increase in the number of infiltrating NK cells (Figure 5A). CD8+ T cells and CD57+ NK cells were spread diffusely throughout the entire sections. To further investigate the differences in the numbers of CD8+ T cells and CD57+ NK cells between CCR5+/+ mice and CCR5−/− mice in immunity-related organ, we also analyzed the CD8 and CD57 reactive cell number in spleen tissues. The number of CD8+ T cells and CD57+ NK cells were higher in the spleen of the CCR5−/− mice than in the spleen of the CCR5+/+ mice (Figure 5B). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in an anti-tumor effect in CCR5−/− mice.\n10.1371/journal.pone.0033747.g005 Figure 5 Induction of the infiltration of CD8+ T cells and NK cells into tumor, and increase in spleen of CCR5−/− mice.\nA and B, Immunolfluorescence analysis was used to determine the expression levels of CD8 (CD8+ cytotoxic T-cell surface marker) and CD57 (NK cell marker) in tumor and spleen sections. The images shown are representative of three separate experiments performed in triplicate. Scale bars indicate 50 µm (A) and 100 µm (B). C and D, Analysis of lymphocyte phenotypes. The tumor and spleen tissues were separated at study termination (Day 31). Flow cytometry analysis was performed using FACSAria flow cytometry, and represent data were shown. Data are means ± S.D. of four experimental animals. To analyze the cell phenotype change in CCR5−/− mice and CCR5+/+ mice by inoculation of the melanoma cell, lymphocytes were isolated from the tumor and spleen tissues. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of CCR5−/− mice tumor tissue were 7.2%, 48.2%, 16.9%, 32.1% and 7.8%, respectively, compared to 2.9%, 11.1%, 2.3%, 0.6% and 3.1% of CCR5+/+ mice (Figure 5C). The lymphocytes that infiltrated the tumor tissue of the CCR5−/− mice also had higher levels of CD19, CD3, CD4, CD8 and CD57 when compared to the CCR5+/+ mice. The B, CD3 T, CD4 T, CD 8 T and NK cell portion of the CCR5−/− mice spleen were 61.3%, 33.4%, 17.6%, 9.2% and 0.6%, respectively compared to 38.3%, 5.9%, 4.0%, 1.0% and 3.9% of the CCR5+/+ mice (Figure 5D). These data suggest that by promoting the infiltration of CD8 T cells and NK cells, which are potent cytotoxic effectors for tumors, could play a role in the inhibition of tumor growth in CCR5−/− mice."}