Transforming growth factor β 1 costimulated growth and regulatory function of staphylococcal enterotoxin B-responsive CD8+ T cells

Abstract

Transforming growth factor β (TGF-β) exhibits diverse effects on growth and differentiation of a wide range of cell types. In the immune system, TGF-β 1 is a potent inhibitor of T cell proliferation and certain T cell effector functions. However, TGF-β 1 also enhances growth of T cells, predominantly of naive phenotype, and induces their expression of selected cytokines. We have previously demonstrated that TGF-β 1 costimulates growth of highly purified murine CD8+ T cells activated by immobilized anti-CD3 Ab. TGF-β 1-costimulated CD8+ T cells rapidly express a memory phenotype, lose lytic function, and express a mixed cytokine pattern with IL-2, IFN-γ, and appreciable IL-10, as well as TGF-β 1. The present work examines the possibility that TGF-β 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-β 1 significantly enhances CD8+ T cell proliferation to SEB in the presence of MHC class II-positive APC and TGF-β 1-primed CD8+ T cells are enriched for SEB-reactive V β 8+ TCR expression. TGF-β 1 priming also up-regulates a memory-like CD45RBlowCD44highMEL-14low phenotype. TGF-β 1 priming inhibits development of SEB-specific lytic effector function by more than 90%. However, TGF-β 1-primed CD8+ effector T cells express elevated levels of IL-10 and TGF-β 1, variable IFN-γ, 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-β 1-primed CD8+ T cells is reversed in part by anti-IL-10 Ab. Thus, in the context of SEB response, TGF-β 1 promotes the outgrowth and induces the effector function of CD8+ T cells that have the capacity to impair T cell clonal growth.

Part of CIRS Nexus · Curated by Lauren Lowenstein, The Biotoxin Lady