Induction of CD4+ regulatory T cells by stimulation with Staphylococcal Enterotoxin C2 through different signaling pathways - 09/10/21
, Yansheng Li a, b, Zhichun Zhang a, b, Wu Gu a, b, Gulinare Halimu a, b, Yuqi Li a, b, Huiwen Zhang a, c, Chenggang Zhang a, cBienvenue sur EM-consulte, la référence des professionnels de santé.
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Abstract |
As a member of superantigens, Staphylococcal Enterotoxin C2 (SEC2) can potently activate T cells expressing specific Vβ repertoires and has been applied in clinic for tumor immunotherapy in China for more than 20 years. However, excessive activation of T cells by over-stimulation with superantigen are always followed by eliciting regulatory T cells (Tregs) induction and functional immunosuppression, which brings uncertainties to SEC2 application in tumor immunotherapy. In this study, we found that SEC2 could induce CD4+CD25+Foxp3+ Tregs from the murine splenocytes in dose and time related manners. The induced Tregs with high expression of GITR and CTLA-4 and low expression of CD127 were TCR Vβ8.2-specific and have character of IL-10 production in a SEC2 dose-depended manner. Importantly, SEC2-induced CD4+ Tregs showed the potent capacity of suppressing proliferation of intact murine splenocytes response to SEC2. Furthermore, by using specific inhibitors or neutralizing antibody, we proved that the signaling pathways of TCR-NFAT/AP-1, IL-2-STAT5, and TGF-β-Smad3 play crucial roles in Tregs induction by SEC2. These findings will help us better understand the balance of immune stimulation and immunosuppression mediated by SEC2 and provide valuable guidance for SEC2 application in antitumor immunology.
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Highlights |
• | SEC2 could induce CD4+CD25+Foxp3+ Tregs in dose- and time-related manners. |
• | SEC2-induced Tregs show the classical phenotypes of regulatory T cells. |
• | SEC2-induced Tregs are TCR Vβ8.2-specific and IL-10 producing. |
• | SEC2-induced Tregs have functional suppressive activity. |
• | TCR-NFAT/AP-1, IL-2-STAT5, and TGF-β-Smad3 are critical for Tregs induction by SEC2. |
Abbreviations : SEC2, Tregs, TCR, GITR, CTLA-4, IL-10, NFAT, AP-1, IL-2, STAT5, TGF-β, APCs, MHC II, Foxp3, RPMI, FBS, CFSE, CHIP
Keywords : Superantigen, SEC2, CD4+ Tregs, Immunosuppression, Foxp3, Tumor immunotherapy
Plan
Vol 143
Article 112204- novembre 2021 Retour au numéro
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