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Science 324 (5934): 1576-1580

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

IL-21R on T Cells Is Critical for Sustained Functionality and Control of Chronic Viral Infection

Anja Fröhlich,1 Jan Kisielow,1 Iwana Schmitz,1 Stefan Freigang,1 Abdijapar T. Shamshiev,1 Jacqueline Weber,1 Benjamin J. Marsland,1 Annette Oxenius,2 Manfred Kopf1,*

Abstract: Chronic viral infection is often associated with the dysfunction of virus-specific T cells. Our studies using Il21r-deficient (Il21r–/–) mice now suggest that interleukin-21 (IL-21) is critical for the long-term maintenance and functionality of CD8+ T cells and the control of chronic lymphocytic choriomeningitis virus infection in mice. Cell-autonomous IL-21 receptor (IL-21R)–dependent signaling by CD8+ T cells was required for sustained cell proliferation and cytokine production during chronic infection. Il21r–/– mice showed normal CD8+ T cell expansion, effector function, memory homeostasis, and recall responses during acute and after resolved infection with several other nonpersistent viruses. These data suggest that IL-21R signaling is required for the maintenance of polyfunctional T cells during chronic viral infections and have implications for understanding the immune response to other persisting antigens, such as tumors.

1 Molecular Biomedicine, Institute of Integrative Biology, ETH Zurich, Switzerland.
2 Institute of Microbiology, ETH Zurich, Switzerland.

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

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