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Production in Developing Th1 Cells through the Repression of Eomesodermin Expression1
* Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115;
Abramson Family Cancer Research Institute and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104; and
Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02115
Exposure of naive Th cell precursors (Thp) to IL-21 inhibits IFN-
production from developing Th1 cells. The inhibition of IFN- seen in IL-21-treated Thp cells is specific as the expression of other Th1 cytokines is unaffected. Recently, it has been reported that Eomesodermin (Eomes), a member of the T-box gene family, is expressed in developing CD8+ T cells and plays an important role in regulating IFN- production and cytolytic effector function. In this study, we show that Eomes mRNA and protein are also expressed in developing Th1 cells, and exposure of naive Thp cells to IL-21 results in a decrease in Eomes expression. Moreover, the repression of Eomes expression by IL-21 is not due to an indirect effect of IL-21 on the expression of IFN- or STAT4 and is independent of STAT1 and T-bet expression. Finally, we show that ectopic expression of Eomes prevents the inhibition of IFN- production from IL-21-treated Thp cells. Taken together, these results demonstrate that Eomes plays a role in regulating IFN- production in CD4+ T cells and IL-21 inhibits IFN- production in developing Th1 cells through the repression of Eomes expression.
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 National Institutes of Health Grants AI42370 (to S.L.R.) and AI40171 (to M.J.G.), and by a gift from the G. Harold and Leila Y. Mathers Charitable Foundation.
2 Current address: National Institute on Aging, Laboratory of Cellular and Molecular Biology, 5600 Nathan Shock Drive, Baltimore, MD 21224.
3 Address correspondence and reprint requests to Dr. Michael J. Grusby, Harvard School of Public Health, Department of Immunology and Infectious Diseases, 651 Huntington Avenue, Building FXB, Room 205, Boston, MA 02115. E-mail address: mgrusby{at}hsph.harvard.edu
4 Abbreviations used in this paper: Eomes, Eomesodermin; CHX, cycloheximide; Thp, Th precursor; WT, wild type.
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