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Regulation of IL-17 in Human CCR6⁺ Effector Memory T Cells¹

Department of Neurology and Neurosciences, University of Medicine and Dentistry New Jersey-New Jersey Medical School, Newark, NJ 07103

IL-17–secreting T cells represent a distinct CD4⁺ effector T cell lineage (Th17) that appears to be essential in the pathogenesis of numerous inflammatory and autoimmune diseases. Although extensively studied in the murine system, human Th17 cells have not been well characterized. In this study, we identify CD4⁺CD45RO⁺CCR7^–CCR6⁺ effector memory T cells as the principal IL-17-secreting T cells. Human Th17 cells have a unique cytokine profile because the majority coexpress TNF- but not IL-6 and a minor subset express IL-17 with IL-22 or IL-17 and IFN-. We demonstrate that the cytokines that promote the differentiation of human naive T cells into IL-17-secreting cells regulate IL-17 production by memory T cells. IL-1β alone or in association with IL-23 and IL-6 markedly increase IL-17⁺ CCR6⁺ memory T cells and induce IL-17 production in CCR6^– memory T cells. We also show that T cell activation induces Foxp3 expression in T cells and that the balance between the percentage of Foxp3⁺ and IL-17⁺ T cells is inversely influenced by the cytokine environment. These studies suggest that the cytokine environment may play a critical role in the expansion of memory T cells in chronic autoimmune diseases.

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 Grant NS34245 from the National Institutes of Health (to C.R.-K.).

² Address correspondence and reprint requests to Dr. Christine Rohowsky-Kochan, University of Medicine and Dentistry New Jersey-New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103. E-mail address: rohowscm{at}umdnj.edu