CD8+ suppressor-mediated regulation of human CD4+ T cell responses to glutamic acid decarboxylase 65.
Although potentially autoreactive T cells are present even in healthy subjects, most individuals do not develop autoimmune disease. It has been well demonstrated that CD4+ CD25+ regulatory T cells play a significant role in controlling the expansion of autoreactive T cells in the periphery. However, some healthy individuals exhibit measurable responses to self peptide even in the presence of CD4+ CD25+ regulatory cells. This article describes the regulation of human CD4+ T cell responses to glutamic acid decarboxylase 65 (GAD65), an autoantigen implicated in type-1 diabetes, by autologous CD8+ suppressor T cells. In cells cultured from healthy individuals, the inclusion of autologous CD8+ T cells at physiological levels resulted in a dramatic decrease in the magnitude of in vitro CD4+ T cell responses to GAD65 peptide. Based on transwell experiments, the observed suppression was cell contact-dependent. However, antibody blocking studies indicated that suppression was mediated by IL-10. Cell fractionation studies suggested that CD8+ suppressor T cells originate from the CD45RA+ CD27- population. The suppression of CD4+ T cell responses to GAD65 in healthy individuals raises the possibility that CD8+ suppressor T cells play an important role in controlling potentially autoreactive T cells in the general population.
James
Eddie A
EA
Benaroya Research Institute at Virginia Mason, Seattle, USA.
Kwok
William W
WW
D001324:Autoantigens / Q000097:blood / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D005968:Glutamate Decarboxylase / Q000097:blood / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007165:Immunosuppression Therapy; D007527:Isoenzymes / Q000097:blood / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000097:blood; D008213:Lymphocyte Activation / Q000276:immunology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000097:blood
D001324:Autoantigens; D016207:Cytokines; D007527:Isoenzymes; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2