PMC:1064873 / 5231-6476 JSONTXT

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{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/1064873","sourcedb":"PMC","sourceid":"1064873","source_url":"http://www.ncbi.nlm.nih.gov/pmc/1064873","text":"CD4+ T cells may be activated by arthritogenic antigens, in conjunction with CD28-mediated costimulatory signaling, in RA. The significance of this autoimmune process has been supported by the linkage of the MHC class II antigens HLA-DRB1*0404 and HLA-DRB1*0401 with disease susceptibility and severity [16,17], and by the high-level expression of MHC class II molecules and both CD28 ligands, CD80 and CD86, in the inflamed ST [18-20]. The continuing emergence of activated CD4+ T cells, even though few in number, may be crucial in sustaining the activation of macrophages and synovial fibroblasts through cell surface signaling by means of cell surface CD69 and CD11, as well as the release of proinflammatory Th1 cytokines such as interferon gamma (IFN)-γ and IL-17 [21,22]. In addition, CD4+ T cells could stimulate B-cell production of autoantibodies such as rheumatoid factor and osteoclast-mediated bone destruction. Their obligatory role in RA synovitis was recently proved by successful treatment of active disease by selective inhibition of T-cell activation with fusion protein of cytotoxic T-cell-associated antigen 4 (CD152)-IgG, which can block the engagement of CD28 on T cells by binding to CD80 and CD86 with high avidity 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