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)-γ production from developing Th1 cells. The repression of IFN-γ 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-γ–producing Th1 cells which could serve to amplify a Th2 response.
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7 October 2002
Article|
September 30 2002
Interleukin 21 Is a T Helper (Th) Cell 2 Cytokine that Specifically Inhibits the Differentiation of Naive Th Cells into Interferon γ–producing Th1 Cells
Andrea L. Wurster,
Andrea L. Wurster
1Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115
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Vikki L. Rodgers,
Vikki L. Rodgers
1Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115
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Abhay R. Satoskar,
Abhay R. Satoskar
2Department of Microbiology, Ohio State University, Columbus, OH 43210
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Matthew J. Whitters,
Matthew J. Whitters
3Wyeth Research, Cambridge, MA 02140
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Deborah A. Young,
Deborah A. Young
3Wyeth Research, Cambridge, MA 02140
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Mary Collins,
Mary Collins
3Wyeth Research, Cambridge, MA 02140
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Michael J. Grusby
Michael J. Grusby
1Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115
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Andrea L. Wurster
1Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115
Vikki L. Rodgers
1Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115
Abhay R. Satoskar
2Department of Microbiology, Ohio State University, Columbus, OH 43210
Matthew J. Whitters
3Wyeth Research, Cambridge, MA 02140
Deborah A. Young
3Wyeth Research, Cambridge, MA 02140
Mary Collins
3Wyeth Research, Cambridge, MA 02140
Michael J. Grusby
1Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115
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: [email protected]
*
Abbreviations used in this paper: DTH, delayed-type hypersensitivity; NK, natural killer; STAT, signal transducer and activator of transcription; Thp, Th precursor.
Received:
April 17 2002
Revision Received:
August 14 2002
Accepted:
August 19 2002
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2002
J Exp Med (2002) 196 (7): 969–977.
Article history
Received:
April 17 2002
Revision Received:
August 14 2002
Accepted:
August 19 2002
Citation
Andrea L. Wurster, Vikki L. Rodgers, Abhay R. Satoskar, Matthew J. Whitters, Deborah A. Young, Mary Collins, Michael J. Grusby; Interleukin 21 Is a T Helper (Th) Cell 2 Cytokine that Specifically Inhibits the Differentiation of Naive Th Cells into Interferon γ–producing Th1 Cells . J Exp Med 7 October 2002; 196 (7): 969–977. doi: https://doi.org/10.1084/jem.20020620
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