title: CTLA-4 regulates tolerance induction and T cell differentiation in vivo.
abstract: Cytotoxic T lymphocyte Ag-4 (CTLA-4; CD152) is an important T cell regulatory molecule. In vitro experiments have shown that the blockade of signals through CTLA-4 augments T cell expansion, while CTLA-4 cross-linking results in decreased T cell proliferation due to decreased IL-2 production. However, less is known about the role of CTLA-4 in regulating an ongoing immune response. In this study, we examined the role of CTLA-4 in the expansion, decline, tolerization, and differentiation of T cells following treatment with staphylococcal enterotoxin B (SEB). Anti-CTLA-4 treatment resulted in increased numbers of SEB-reactive T cells and blockade of subsequent tolerance induction. Further examination of the SEB-reactive cells from anti-CTLA-4-treated mice demonstrated that both the CD4+ and CD8+ Vbeta8+ T cells produced IL-4, providing evidence that not only do signals through CTLA-4 regulate T cell-tolerizing events, but they also play an important role in the differentiation of T cells in vivo.
authors.affiliation: The Committee on Immunology and the Ben May Institute for Cancer Research, The University of Chicago, IL 60637, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Walunas
authors.forename: J A
authors.initials: JA
authors.lastname: Bluestone
mesh_terms: D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D060908:CTLA-4 Antigen; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division; D004768:Enterotoxins / Q000276:immunology; D005260:Female; D007108:Immune Tolerance; D018796:Immunoconjugates; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D004768:Enterotoxins; D018796:Immunoconjugates; D015847:Interleukin-4; C031818:enterotoxin B, staphylococcal; D000069594:Abatacept; D007371:Interferon-gamma