Cutting edge: control of CD8+ T cell activation by CD4+CD25+ immunoregulatory cells.
CD4(+)CD25(+) regulatory T cells inhibit organ-specific autoimmune diseases induced by CD4(+)CD25(-) T cells and are potent suppressors of CD4(+)CD25(-) T cell activation in vitro. We demonstrate that CD4(+)CD25(+) T cells also suppress both proliferation and IFN-gamma production by CD8(+) T cells induced either by polyclonal or Ag-specific stimuli. CD4(+)CD25(+) T cells inhibit the activation of CD8(+) responders by inhibiting both IL-2 production and up-regulation of IL-2Ralpha-chain (CD25) expression. Suppression is mediated via a T-T interaction as activated CD4(+)CD25(+) T cells suppress the responses of TCR-transgenic CD8(+) T cells stimulated with soluble peptide-MHC class I tetramers in the complete absence of APC. These results broaden the immunoregulatory role played by CD4(+)CD25(+) T cells in the prevention of autoimmune diseases, but also raise the possibility that they may hinder the induction of effector CD8(+) T cells to tumor or foreign Ags.
Piccirillo
C A
CA
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
Shevach
E M
EM
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2