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Cutting Edge: A Regulatory T Cell-Dependent Novel Function of CD25 (IL-2R) Controlling Memory CD8⁺ T Cell Homeostasis¹

Division of Rheumatology and Immunology, Department of Internal Medicine, University of Virginia, Charlottesville, VA 22908

A massive systemic expansion of CD8⁺ memory T (T_M) cells and a remarkable increase in circulating IL-2 were observed only in IL-2R (CD25) knockout (KO) mice but not in IL-2 KO and scurfy mice, although all three mutants lack regulatory T (Treg) cells. However, both phenotypes were suppressed by the transfer of Treg cells. The data presented indicate that Treg cell deficiency drives naive T cells to T_M cells. The lack of high-affinity IL-2R in IL-2R KO mice increases circulating IL-2 that is then preferentially used by CD8⁺ T_M cells through its abundant low-affinity IL-2R, resulting in systemic CD8⁺ T_M cell dominance. Our study demonstrates the critical control of CD8⁺ T_M cell homeostasis by a Treg cell-dependent novel function of CD25 and resolves its mechanism of action.

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 AI-036938, DE-017579 and AR-051203 (to S.-T.J.), AR-045222, AR-047988 and AR-049449 (to S.M.F.), HL-70065 (to S.-S.J.S.), AR-051391 (to U.S.D.), and DK-059850 (to W.N.J.).

² S.M.F. and S.-T.J. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Shyr-Te Ju, Division of Rheumatology and Immunology, Department of Internal Medicine, P.O. Box 800412, Old Medical School Building, Room 5777, University of Virginia, Charlottesville, VA 22908-0412. E-mail address: sj8r{at}virginia.edu

⁴ Abbreviations used in this paper: Treg, regulatory T; KO, knockout; T_M, memory T; T_N, naive T.

⁵ Both CD8⁺ and CD4⁺ T cells were increased in scurfy mice but their ratios were maintained in a normal range.

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