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IL-23 Promotes the Production of IL-17 by Antigen-Specific CD8 T Cells in the Absence of IL-12 and Type-I Interferons¹

Meredith M. Curtis^*, Sing Sing Way and Christopher B. Wilson^2,*

^* Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195; and Departments of Pediatrics and Microbiology, University of Minnesota School of Medicine, Minneapolis, MN 55455

In contrast to CD4 T cells, CD8 T cells inherently differentiate into IFN--producing effectors. Accordingly, while generation of IFN--producing Th1 CD4 T cells was profoundly impaired in mice deficient for both type-I IFN and IL-12 signaling in response to infection with Listeria monocytogenes, generation of Ag-specific, IFN--producing CD8 T cells was unimpaired. However, a fraction of these CD8 T cells also produced IL-17 in an IL-23-dependent manner. Furthermore, the addition of IL-23 in vitro was sufficient for some naive CD8 T cells to differentiate into IFN-/IL-17 dual-producing cells and was associated with increased expression of ROR-t and ROR-. Addition of IL-6 and TGF-β to IL-23 further augmented ROR-t and ROR- expression and suppressed Eomes expression, thereby enhancing IL-17 production by CD8 T cells. A loss of cytotoxic function accompanied the production of IL-17, as the addition of IL-6 and TGF-β resulted in a marked reduction of granzyme B and perforin expression. Thus, CD8 T cells retain sufficient plasticity to respond to environmental cues and can acquire additional effector functions in response to their environmental context.

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 in part by an Infectious Diseases Society of America Career Development Award (to S.S.W.), a March of Dimes Basil O'Connor Research Award (to S.S.W.), and National Institutes of Health Grants T32 CA009537 and T32 GM07270 (to M.M.C.), K08HD51584 (to S.S.W.), and R01 HD18184 (to C.B.W.).

² Address correspondence and reprint requests to Dr. Christopher B. Wilson, Department of Immunology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195-7650. E-mail address: cbwilson{at}u.washington.edu

³ Abbreviations used in this paper: Lm, Listeria monocytogenes; DKO, double knockout; WT, wild type; KO, knockout; Tg, transgenic; CFU, colony forming unit.