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Regulatory T Cells Dynamically Control the Primary Immune Response to Foreign Antigen¹

Dipica Haribhai^*, Wen Lin, Lance M. Relland^*, Nga Truong, Calvin B. Williams^2,* and Talal A. Chatila^2,

^* Division of Rheumatology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226; and Division of Immunology, Allergy and Rheumatology, Department of Pediatrics, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, CA 90095

The population dynamics that enable a small number of regulatory T (T_R) cells to control the immune responses to foreign Ags by the much larger conventional T cell subset were investigated. During the primary immune response, the expansion and contraction of conventional and T_R cells occurred in synchrony. Importantly, the relative accumulation of T_R cells at peak response significantly exceeded that of conventional T cells, reflecting extensive cell division within the T_R cell pool. Transfer of a polyclonal T_R cell population before immunization antagonized both polyclonal and TCR transgenic responses, whereas blocking T_R cell function enhanced those responses. These results define an inverse quantitative relationship between T_R and conventional T cells that controls the magnitude of the primary immune response. The high frequency of dividing T_R cells suggests degenerate TCR specificity enabling activation by a broad spectrum of Ags.

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 2R01AI065617 (to T.A.C.) and R01 AI47154 (to C.B.W.), and by the Nickolett Family Foundation and the D.B. and Marjorie Reinhart Family Foundation (to C.B.W.).

² Address correspondence and reprint requests to Dr. Talal A. Chatila, Division of Immunology, Allergy and Rheumatology, Department of Pediatrics, The David Geffen School of Medicine at the University of California at Los Angeles, MDCC 12-430, 10833 Le Conte Avenue, Los Angeles, CA 90095; E-mail address: tchatila{at}mednet.ucla.edu or Dr. Calvin B. Williams, Division of Rheumatology, Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226; E-mail address: cwilliam{at}mcw.edu

³ Abbreviations used in this paper: T_R, regulatory T; EGFP, enhanced GFP; IRES, internal ribosomal entry sequence; WT, wild type; R, responder cell; S, suppressor cell.

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