Mechanism of immunosuppression by staphylococcal superantigen.

Journal Club talk presented by Keun Seok Seo, an Assistant Professor in the College of Veterinary Medicine, Mississippi State University

Superantigens (SAgs) produced by S. aureus induce proliferation of T cells bearing specific TCR Vß sequences and massive cytokinemia that cause toxic shock syndrome at high concentrations. However, the biological relevance of SAgs produced at very low concentrations during asymptomatic colonization or chronic infections is not understood. In this study, we demonstrated that suboptimal stimulation of human PBMCs with a low concentration (1 ng/ml) of staphylococcal enterotoxin C1 (SEC1), at which half-maximal T cell proliferation was observed, induced CD8+CD25+ T cells expressing markers related to regulatory T cells (Tregs)  such as IFN-?, IL-10, TGF-?, FOXP3+, CD28+, CTLA4+, TNFR2+, CD45RO+, and HLA-DR+.  Importantly, the mechanism by which these CD8+CD25+ T cells suppressed responder cell proliferation was contact-dependent and soluble factor-dependent, involving galectin-1 and granzymes, respectively. By contrast, optimal stimulation of human PBMCs with a high concentration (1 µg/ml) of SEC1, at which maximal T cell proliferation was observed, also induced similar expression of markers related to Tregs including FOXP3 in CD8+CD25+ cells, but these T cells were not functionally immunosuppressive. We further demonstrated that SAg induced TCR V?- and MHC II-restricted expansion of immunosuppressive CD8+CD25 T cells independent from CD4+ T cells. Our results suggest that the concentration of SAg remarkably affects the functional characteristics of activated T cells, and low concentrations of SAg produced during asymptomatic colonization or chronic S. aureus infection induce immunosuppressive CD8+ regulatory T cells, potentially promoting colonization, propagation, and invasion of S. aureus in the host.