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Cutting Edge: A T-bet-Independent Role for IFN-/β in Regulating IL-2 Secretion in Human CD4⁺ Central Memory T Cells¹

Ann M. Davis^*, Hilario J. Ramos^*, Laurie S. Davis^, and J. David Farrar^2,*,

^* Department of Immunology, Department of Rheumatology, Department of Internal Medicine, and Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390

IL-2 is a hallmark cytokine secreted by central memory CD4⁺ T cells (T_CM). Although naive cells rapidly secrete IL-2 in response to Ag stimulation, IL-12 inhibits IL-2 secretion in daughter cells as they differentiate into Th1 cells. In this study, we uncover a unique role for IFN- in regulating IL-2 secretion by human T_CM cells. IFN- synergized with IL-12 to enhance a subset of cells that secreted high and sustained levels of IL-2. These IL-2-secreting cells displayed phenotypic and functional characteristics of T_CM and were capable of generating IFN--secreting effectors upon secondary activation. T-bet has been implicated in negatively regulating IL-2 secretion in murine T cells; however, T-bet expression did not inhibit IFN--dependent IL-2 secretion in human T_CM cells. Thus, our results highlight a unique role for IFN- in regulating the development of IL-2-secreting human T_CM cells.

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/National Institute of Allergy and Infectious Diseases Grant AI056222 (to J.D.F.). A.M.D. was supported by NIH/National Institute of General Medical Sciences Training Grant GM00820317, and H.J.R. was supported by National Institutes of Health/National Institute of Allergy and Infectious Diseases Predoctoral Fellowship Grant AI068622.

² Address correspondence and reprint requests to Dr. J. David Farrar, Department of Immunology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9093. E-mail address: David.Farrar{at}UTSouthwestern.edu

³ Abbreviations used in this paper: T_EM, effector memory T cell; 7-AAD, 7-aminoactinomycin D; cIMDM, complete IMDM; T_CM, central memory T cell.

⁴ The online version of this article contains supplemental material.