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Published Online May 7, 2009
Science DOI: 10.1126/science.1174182

Reports

Submitted on March 27, 2009
Accepted on April 28, 2009

IL-21 Is Required to Control Chronic Viral Infection

Heidi Elsaesser 1, Karsten Sauer 2, David G. Brooks 1*

1 Department of Microbiology, Immunology and Molecular Genetics and the UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
2 Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, CA 92037, USA.

* To whom correspondence should be addressed.
David G. Brooks , E-mail: dbrooks{at}em.ucla.edu

CD4+ and CD8+ T cell functions are rapidly aborted during chronic infection, preventing viral clearance. CD4+ T cell help is required throughout chronic infection to sustain CD8 T cell responses; however, the necessary factor(s) provided by CD4+ T cells are currently unknown. Using a mouse model of chronic viral infection, we demonstrate that interleukin-21 (IL-21) is an essential component of CD4+ T cell help. In the absence of IL-21 signaling, despite elevated CD4+ T cell responses, CD8+ T cell responses are severely impaired. CD8+ T cells directly require IL-21 to avoid deletion, maintain immunity, and resolve persistent infection. Thus, IL-21 specifically sustains CD8+ T cell effector activity and provides a mechanism of CD4+ T cell help during chronic virus infection.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Endogenous IL-21 Restricts CD8+ T Cell Expansion and Is not Required for Tumor Immunity.
H. Sondergaard, J. M. Coquet, A. P. Uldrich, N. McLaughlin, D. I. Godfrey, P. V. Sivakumar, K. Skak, and M. J. Smyth (2009)
J. Immunol. 183, 7326-7336
   Abstract »    Full Text »    PDF »
A Little 'Help' from IL-21 During Persistent Viral Infection.
D. B. McGavern (2009)
J Mol Cell Biol
   Abstract »    Full Text »    PDF »
A Chronic Need for IL-21.
L. D. S. Johnson and S. C. Jameson (2009)
Science 324, 1525-1526
   Abstract »    Full Text »    PDF »


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Science. ISSN 0036-8075 (print), 1095-9203 (online)