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

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 cho...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2009-06, Vol.324 (5934), p.1576-1580
Main Authors: Fröhlich, Anja, Kisielow, Jan, Schmitz, Iwana, Freigang, Stefan, Shamshiev, Abdijapar T, Weber, Jacqueline, Marsland, Benjamin J, Oxenius, Annette, Kopf, Manfred
Format: Article
Language:English
Subjects:
Animals
Antivirals
Biological and medical sciences
CD8-Positive T-Lymphocytes - immunology
Cellular biology
Chronic Disease
Chronic illnesses
Cytokines
Dosage
Humans
Immune system
Immunity
Immunologic Memory
Infections
Infectious diseases
Interferon-gamma - biosynthesis
Lymphocytes
Lymphocytic Choriomeningitis - immunology
Lymphocytic choriomeningitis virus
Medical sciences
Mice
Mice, Inbred C57BL
Peptide Fragments - biosynthesis
Proteins
Receptors
Receptors, Interleukin-21 - immunology
Signal Transduction
T lymphocytes
Viral diseases
Viral infections
Viruses
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1172815