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Published Online May 28, 2009
Science DOI: 10.1126/science.1172815

Reports

Submitted on February 26, 2009
Accepted on May 20, 2009

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 Kopf 1*

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

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

Chronic viral infection is often associated with dysfunction of virus specific T cells. Our studies using Il21r-deficient (Il21r–/–) mice now suggest that interleukin (IL)-21 is critical for long-term maintenance and functionality of CD8+ T cells and 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 proliferation and cytokine production during chronic infection. Notably, 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.


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