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Science 324 (5934): 1572-1576

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

A Vital Role for Interleukin-21 in the Control of a Chronic Viral Infection

John S. Yi, Ming Du, Allan J. Zajac*

Abstract: Understanding the factors that regulate the induction, quality, and longevity of antiviral T cell responses is essential for devising rational strategies to prevent or combat infections. In this study, we show that interleukin-21 (IL-21), likely produced by CD4+ T cells, directly influences the generation of polyfunctional CD8+ T cells and that the number of CD4+ T cells that produce IL-21 differs markedly between acute and chronic infections. IL-21 regulates the development of CD8+ T cell exhaustion and the ability to contain chronic lymphocytic choriomeningitis virus infection. Thus, IL-21 serves as a critical helper factor that shapes the functional quality of antiviral CD8+ T cells and is required for viral control.

Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294–2170, USA.

* To whom correspondence should be addressed. E-mail: azajac{at}

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