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Science 324 (5934): 1569-1572

Copyright © 2009 by the American Association for the Advancement of Science

IL-21 Is Required to Control Chronic Viral Infection

Heidi Elsaesser,1 Karsten Sauer,2 David G. Brooks1,*

Abstract: CD4+ and CD8+ T cell functions are rapidly aborted during chronic infection, preventing viral clearance. CD4+ T cell help is required throughout chronic infection so as 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 demonstrated 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 viral infection.

1 Department of Microbiology, Immunology, and Molecular Genetics and University of California, Los Angeles (UCLA) AIDS Institute, David Geffen School of Medicine, UCLA, 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. E-mail: dbrooks{at}em.ucla.edu


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