{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T18:58:31Z","timestamp":1788980311718,"version":"build-2803163510"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Superantigens (SAgs) produced by Staphylococcus aureus at high concentrations induce proliferation of T cells bearing specific TCR V\u03b2 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-\u03b3, IL-10, TGF-\u03b2, 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\u2013dependent manners, involving galectin-1 and granzymes, respectively. In contrast, optimal stimulation of human PBMCs with a high concentration (1 \u03bcg\/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 V\u03b2\u2013restricted and MHC class II\u2013restricted 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.<\/jats:p>","DOI":"10.4049\/jimmunol.1602109","type":"journal-article","created":{"date-parts":[[2017,12,13]],"date-time":"2017-12-13T15:50:19Z","timestamp":1513180219000},"page":"669-680","source":"Crossref","is-referenced-by-count":33,"title":["Induction of Immunosuppressive CD8+CD25+FOXP3+ Regulatory T Cells by Suboptimal Stimulation with Staphylococcal Enterotoxin C1"],"prefix":"10.1093","volume":"200","author":[{"given":"Juyeun","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University , Mississippi State, MS 39762"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nogi","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University , Mississippi State, MS 39762"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8375-0178","authenticated-orcid":false,"given":"Joo Youn","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University , Mississippi State, MS 39762"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara L F","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University , Mississippi State, MS 39762"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4574-5965","authenticated-orcid":false,"given":"Stephen B","family":"Pruett","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University , Mississippi State, MS 39762"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4610-6893","authenticated-orcid":false,"given":"Juw Won","family":"Park","sequence":"additional","affiliation":[{"name":"Kentucky Biomedical Research Infrastructure Network Bioinformatics Core, Department of Computer Engineering and Computer Science, University of Louisville , Louisville, KY 40292"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong Ho","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Microbiology, BK21 Program for Veterinary Science, College of Veterinary Medicine, Seoul National University , Seoul 151-742,","place":["South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9280-9680","authenticated-orcid":false,"given":"Keun Seok","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University , Mississippi State, MS 39762"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,1,15]]},"reference":[{"key":"2025030610010598000_r1","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.3201\/eid1312.070629","article-title":"Hospitalizations and deaths caused by methicillin-resistant Staphylococcus aureus, United States, 1999-2005","volume":"13","author":"Klein","year":"2007","journal-title":"Emerg. 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