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Cutting Edge: Regulatory T Cells Do Not Require Stimulation through Their TCR to Suppress¹

Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105

The mechanism and stimulatory requirements of regulatory T cell (Treg)-mediated suppression are still unclear. To assess the requirement for Treg stimulation by cognate peptide:MHC, we used T cells from OTII and AND TCR transgenic mice that are specific for and restricted by distinct, noncrossreactive peptide:MHC combinations. This allowed us to independently activate Tregs and their conventional T cell (Tconv) targets. Surprisingly, we found that suppression can occur in the absence of peptide:MHC-mediated stimulation of Tregs. This suppression was Treg dependent and not due to cold target inhibition. Using Rag1^–/– TCR transgenic T cells, we show that regulation of Tconv proliferation by heterogeneous Tregs is not due to alloreactivity or crossreactivity. Finally, using anti-TCR-Vβ8-coated microbeads and Vβ8^– Tregs, we show that TCR stimulation-independent suppression can occur in the absence of APCs. These data suggest that Tregs may possess constitutive regulatory activity that can be mediated in the absence of cognate peptide:MHC-TCR stimulation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants AI39480 and AI058156, St. Jude Cancer Center Support Center of Research Excellence Grant CA-21765, and the American Lebanese Syrian Associated Charities.

² Address correspondence and reprint request to Dr. Dario Vignali, Department of Immunology, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678. E-mail address: vignali.lab{at}stjude.org

³ Abbreviations used in this paper: Treg, regulatory T cell; DC, dendritic cell; PCC, pigeon cytochrome c; Tconv, conventional T cell.

⁴ The online version of this article contains supplemental material.