Id |
Subject |
Object |
Predicate |
Lexical cue |
T317 |
0-15 |
Sentence |
denotes |
T Cell Response |
T318 |
16-229 |
Sentence |
denotes |
Generation of early adaptive immune response is critical for the selective elimination of virus-infected cells and neutralization of viral antigens, thereby preventing the damage to the underlying lung parenchyma. |
T319 |
230-435 |
Sentence |
denotes |
Cytokines, chemokines, PAMPs, and DAMPs released by infected ATII and activated AMs in the lung are adequate to mount a well-coordinated and regulated adaptive immune response by priming lung resident DCs. |
T320 |
436-554 |
Sentence |
denotes |
After encountering the antigen-presenting DCs, naive CD4+ T cells differentiate into effector and memory CD4+ T cells. |
T321 |
555-777 |
Sentence |
denotes |
At least five different CD4+ T cell lineages are known (TH1, TH2, TH17, TFH, and TREG cells) with prominent roles of TH1 and TFH cells in mounting antiviral response during SARS-CoV infection (Channappanavar et al., 2014). |
T322 |
778-887 |
Sentence |
denotes |
Additionally, some studies have also shown a functional TH2 response in PBMCs derived from COVID-19 patients. |
T323 |
888-1021 |
Sentence |
denotes |
Release of TH2 specific cytokines like IL-4 and IL-5 was observed in vitro after these cells were stimulated (Weiskopf et al., 2020). |
T324 |
1022-1169 |
Sentence |
denotes |
Similarly, these patients show enhanced production of IL-17 along with other TH17 cell-specific cytokines (Liu J. et al., 2020; Wu and Yang, 2020). |
T325 |
1170-1376 |
Sentence |
denotes |
These findings suggest that the TH cell response in COVID-19 patients is complex concerning other infections, and this complexity may partly depend upon the prevailing pathophysiological state of a patient. |
T326 |
1377-1541 |
Sentence |
denotes |
During viral infections like SARS-CoV, TH1 differentiation is influenced by IL-12 and IFN-γ secreted by DCs along with co-stimulatory signaling via B7-1/2 and CD28. |
T327 |
1542-1679 |
Sentence |
denotes |
Whereas IL-6 secreted by DCs influence TFH differentiation to aid in antibody secretion by B cells (Tang et al., 2008; Lau et al., 2012). |
T328 |
1680-1937 |
Sentence |
denotes |
Under the influence of chemokines (CCL3, CCL4, CCL5, CCL8), TH1 cells are recruited to the site of infection and are distinguished by the secretion of IL-2, IFN-γ, IL-12, and TNF-α as the main effector cytokines during SARS-CoV infections (Li et al., 2008). |
T329 |
1938-2109 |
Sentence |
denotes |
Similarly, naive CD8+ T cells are activated by DCs by engaging MHC-I and TCR receptors, along with CD28-B7 co-stimulatory signaling and cytokines released by CD4+ T cells. |
T330 |
2110-2258 |
Sentence |
denotes |
IL-2 secreted chiefly by CD4+ T cells is also implicated in their long-term maintenance and proliferation (Eickhoff et al., 2015; Hor et al., 2015). |
T331 |
2259-2435 |
Sentence |
denotes |
Notably, CD8+ T cells could also be activated independently of help from CD4+ T cells under conditions where a robust IFN Type I response is present (Wiesel and Oxenius, 2012). |
T332 |
2436-2652 |
Sentence |
denotes |
These activated CD8+ T cells [also referred to as cytotoxic T lymphocytes (CTLs)] get subsequently recruited to the effector organ under the influence of chemokines (CCL3, CCL4, CCL5, CXCL9, and CXCL10) (Nolz, 2015). |
T333 |
2653-2852 |
Sentence |
denotes |
At the infected site, CTLs mount an antiviral response by directly killing the infected cells via secretion of cytotoxic molecules like granzymes, perforins, granulysin, and other cytotoxic granules. |
T334 |
2853-3100 |
Sentence |
denotes |
Very recently, a study shows that CTLs secrete the granzymes and perforins as supramolecular attack particles (SMAPs) in a glycoprotein complex along with over 283 other proteins (including cytokines such as IFN-γ and TNF-α) (Bálint et al., 2020). |
T335 |
3101-3202 |
Sentence |
denotes |
It will be interesting to know whether infection by CoVs also influences the release of SMAP by CTLs. |
T336 |
3203-3344 |
Sentence |
denotes |
Animal studies have revealed the critical molecular insights of CD4+ cells in SARS-CoV clearance and attenuation of a pathological condition. |
T337 |
3345-3484 |
Sentence |
denotes |
The depletion of CD4+ cells was associated with reduced virus clearance and interstitial pneumonitis (Jin et al., 2005; Wang et al., 2006). |
T338 |
3485-3610 |
Sentence |
denotes |
In comparison, the adoptive transfer of virus-specific CD4+ and CD8+ T cells resulted in viral clearance (Zhao et al., 2010). |
T339 |
3611-3827 |
Sentence |
denotes |
Similarly, clinical data has consistently shown the presence of antigen-specific CD4+ and CD8+ T cells in the recovered patients, akin to what was found in immunized animals, reviewed in Channappanavar et al. (2014). |
T340 |
3828-3964 |
Sentence |
denotes |
On the other hand, severe cases of SARS-CoV infection were associated with a decline in T cells, as will be discussed in later sections. |
T341 |
3965-4138 |
Sentence |
denotes |
Thus, based on these animal and clinical data, CD4+ T and CD8+ T cells were central to the antiviral response during SARS-CoV infection (Peng et al., 2006; Oh et al., 2012). |
T342 |
4139-4254 |
Sentence |
denotes |
A subset of primed CD4+ and CD8+ T cells differentiates into long-acting memory cells after the infection subsides. |
T343 |
4255-4428 |
Sentence |
denotes |
TCR-p: MHCII signaling helps in CD4+ T memory cell formation along with presence of cytokines like IL-2, IL-21 and interaction via CD40R-CD40L (Jaigirdar and MacLeod, 2015). |
T344 |
4429-4576 |
Sentence |
denotes |
Similarly, This CD8+ T cell transition to memory cells take place under the influence of CD8+ TREG cells via secreted IL-10 (Laidlaw et al., 2015). |
T345 |
4577-4714 |
Sentence |
denotes |
Long lasting CD4+ and CD8+ T memory cells were detected in the recovered SARS-CoV infected patients (Peng et al., 2006; Li et al., 2008). |
T346 |
4715-4875 |
Sentence |
denotes |
Besides, other T cells subsets which are involved in antiviral response include unconventional NKT cells (CD56+) and MAIT (mucosa-associated invariant T) cells. |
T347 |
4876-5045 |
Sentence |
denotes |
NKT cells act at the interface between innate and adaptive immune response and traffic to the site of infection under the influence of cytokines (Tsay and Zouali, 2018). |
T348 |
5046-5154 |
Sentence |
denotes |
MAIT cells reside in the mucosal lining, such as in the lungs where they serve an immunoregulatory function. |
T349 |
5155-5297 |
Sentence |
denotes |
Both these cell types play an essential role in the early clearance of the SARS-CoV-2, along with other T cell subsets (Grifoni et al., 2020). |
T350 |
5298-5408 |
Sentence |
denotes |
Strategies to enhance their function are proposed to enhance the virial clearance during COVID-19 (Cao, 2020). |
T351 |
5409-5579 |
Sentence |
denotes |
Role of these cells will be further discussed under the dysfunctional immune response in section “T and B Cell Response in Mild/Moderate and Recovered COVID-19 Patients.” |