Induction of Immunosuppressive CD8+CD25+FOXP3+ Regulatory T Cells by Suboptimal Stimulation with Staphylococcal Enterotoxin C1

ORCID

Park (Joo Youn): https://orcid.org/0000-0002-8375-0178; Kaplan: https://orcid.org/0000-0002-1992-4145; Pruett: https://orcid.org/0000-0003-4574-5965; Park (Juw Won): https://orcid.org/0000-0002-4610-6893; Seo: https://orcid.org/0000-0001-9280-9680

MSU Affiliation

College of Veterinary Medicine; Department of Basic Sciences

Creation Date

2026-03-30

Abstract

Superantigens (SAgs) produced by Staphylococcus aureus at high concentrations induce proliferation of T cells bearing specific TCR Vb sequences and massive cytokinemia that cause toxic shock syndrome. However, the biological relevance of SAgs produced at very low concentrations during asymptomatic colonization or chronic infections is not understood. In this study, we demonstrate that suboptimal stimulation of human PBMCs with a low concentration (1 ng/ml) of staphylococcal enterotoxin C1, 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-γ, IL-10, TGF-β, FOXP3, CD28, CTLA4, TNFR2, CD45RO, and HLA-DR. Importantly, these CD8+CD25+ T cells suppressed responder cell proliferation mediated in contact-dependent and soluble factor-dependent manners, involving galectin-1 and granzymes, respectively. In contrast, optimal stimulation of human PBMCs with a high concentration (1 mg/ml) of staphylococcal enterotoxin C1, 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 Vb-restricted and MHC class II-restricted expansion of immunosuppressive CD8+CD25+ T cells is independent of CD4+ T cells. Our results suggest that the concentration of SAg strongly 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+ Tregs, potentially promoting colonization, propagation, and invasion of S. aureus in the host.

Publication Date

1-15-2018

Publication Title

Journal of Immunology

Publisher

American Association of Immunologists; Oxford University Press

First Page

669

Last Page

680

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Digital Object Identifier (DOI)

https://doi.org/10.4049/jimmunol.1602109