The Journal of Experimental Medicine
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Published online 30 September 2002 doi:10.1084/jem.20020620
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© Rockefeller University Press, 0022-1007/2002/10/969/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 7, October 7, 2002 969-977
Interleukin 21 Is a T Helper (Th) Cell 2 Cytokine that Specifically Inhibits the Differentiation of Naive Th Cells into Interferon {gamma}–producing Th1 Cells

Andrea L. Wurster1, Vikki L. Rodgers1, Abhay R. Satoskar2, Matthew J. Whitters3, Deborah A. Young3, Mary Collins3 and Michael J. Grusby1

1 Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115
2 Department of Microbiology, Ohio State University, Columbus, OH 43210
3 Wyeth Research, Cambridge, MA 02140

Address correspondence to Michael J. Grusby, Dept. of Immunology and Infectious Diseases, 651 Huntington Ave., Boston, MA 02115. Phone: 617-432-1240; Fax: 617-432-0084; E-mail: mgrusby{at}hsph.harvard.edu

The cytokine potential of developing T helper (Th) cells is directly shaped both positively and negatively by the cytokines expressed by the effector Th cell subsets. Here we find that the recently identified cytokine, interleukin (IL)-21, is preferentially expressed by Th2 cells when compared with Th1 cells generated in vitro and in vivo. Exposure of naive Th precursors to IL-21 inhibits interferon (IFN)-{gamma} production from developing Th1 cells. The repression of IFN-{gamma} production is specific in that the expression of other Th1 and Th2 cytokines is unaffected. IL-21 decreases the IL-12 responsiveness of developing Th cells by specifically reducing both signal transducer and activator of transcription 4 protein and mRNA expression. These results suggest that Th2 cell-derived IL-21 regulates the development of IFN-{gamma}–producing Th1 cells which could serve to amplify a Th2 response.

Key Words: cytokines • T lymphocytes helper inducer • cell differentiation • immunosuppression • interleukins


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