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Originally published in Science Express on 28 May 2009
Science 19 June 2009:
Vol. 324. no. 5934, pp. 1576 - 1580
DOI: 10.1126/science.1172815
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Reports

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,*

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}ethz.ch

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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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