title: Transforming growth factor beta 1 costimulated growth and regulatory function of staphylococcal enterotoxin B-responsive CD8+ T cells.
abstract: Transforming growth factor beta (TGF-beta) exhibits diverse effects on growth and differentiation of a wide range of cell types. In the immune system, TGF-beta 1 is a potent inhibitor of T cell proliferation and certain T cell effector functions. However, TGF-beta 1 also enhances growth of T cells, predominantly of naive phenotype, and induces their expression of selected cytokines. We have previously demonstrated that TGF-beta 1 costimulates growth of highly purified murine CD8+ T cells activated by immobilized anti-CD3 Ab. TGF-beta 1-costimulated CD8+ T cells rapidly express a memory phenotype, lose lytic function, and express a mixed cytokine pattern with IL-2, IFN-gamma, and appreciable IL-10, as well as TGF-beta 1. The present work examines the possibility that TGF-beta 1 similarly costimulates response of murine CD8+ T cells to the microbial superantigen staphylococcal enterotoxin B (SEB) and characterizes their effector and regulatory functions. TGF-beta 1 significantly enhances CD8+ T cell proliferation to SEB in the presence of MHC class II-positive APC and TGF-beta 1-primed CD8+ T cells are enriched for SEB-reactive V beta 8+ TCR expression. TGF-beta 1 priming also up-regulates a memory-like CD45RBlowCD44highMEL-14low phenotype. TGF-beta 1 priming inhibits development of SEB-specific lytic effector function by more than 90%. However, TGF-beta 1-primed CD8+ effector T cells express elevated levels of IL-10 and TGF-beta 1, variable IFN-gamma, and undetectable IL-4. Additionally, they exhibit growth inhibitory effector function of SEB-induced proliferation of other CD4+ and CD8+ T cells. Growth inhibition by TGF-beta 1-primed CD8+ T cells is reversed in part by anti-IL-10 Ab. Thus, in the context of SEB response, TGF-beta 1 promotes the outgrowth and induces the effector function of CD8+ T cells that have the capacity to impair T cell clonal growth.
authors.affiliation: Department of Microbiology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: S
authors.initials: S
authors.lastname: Rich
authors.forename: M
authors.initials: M
authors.lastname: Seelig
authors.forename: H M
authors.initials: HM
authors.lastname: Lee
authors.forename: J
authors.initials: J
authors.lastname: Lin
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D003602:Cytotoxicity, Immunologic; D004768:Enterotoxins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D015398:Signal Transduction / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D004768:Enterotoxins; D018089:Superantigens; D016212:Transforming Growth Factor beta; C031818:enterotoxin B, staphylococcal