CD8+ T cells control the TH phenotype of MBP-reactive CD4+ T cells in EAE mice.
Trimolecular interactions between the T cell antigen receptor and MHC/peptide complexes, together with costimulatory molecules and cytokines, control the initial activation of naive T cells and determine whether the helper precursor cell differentiates into either T helper (TH)1 or TH2 effector cells. We now present evidence that regulatory CD8(+) T cells provide another level of control of TH phenotype during further evolution of immune responses. These regulatory CD8(+) T cells are induced by antigen-triggered CD4(+) TH1 cells during T cell vaccination and, in vitro, distinguish mature TH1 from TH2 cells in a T cell antigen receptor Vbeta-specific and Qa-1-restricted manner. In vivo, protection from experimental autoimmune encephalomyelitis (EAE) induced by T cell vaccination depends on CD8(+) T cells, and myelin basic protein-reactive TH1 Vbeta8(+) clones, but not TH2 Vbeta8(+) clones, used as vaccine T cells, protect animals from subsequent induction of EAE. Moreover, in vivo depletion of CD8(+) T cells during the first episode of EAE results in skewing of the TH phenotype toward TH1 upon secondary myelin basic protein stimulation. These data provide evidence that CD8(+) T cells control autoimmune responses, in part, by regulating the TH phenotype of self-reactive CD4(+) T cells.
Jiang
H
H
College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. hj4@columbia.edu
Braunstein
N S
NS
Yu
B
B
Winchester
R
R
Chess
L
L
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000097:blood / Q000276:immunology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006825:Hybridomas; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D004676:Myelin Basic Protein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D004676:Myelin Basic Protein; D010446:Peptide Fragments; C032907:Q surface antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; C074815:myelin basic protein 1-9; D015847:Interleukin-4; D007371:Interferon-gamma