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 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.
Fröhlich
Anja
A
Molecular Biomedicine, Institute of Integrative Biology, ETH Zurich, Switzerland.
Kisielow
Jan
J
Schmitz
Iwana
I
Freigang
Stefan
S
Shamshiev
Abdijapar T
AT
Weber
Jacqueline
J
Marsland
Benjamin J
BJ
Oxenius
Annette
A
Kopf
Manfred
M
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000096:biosynthesis; D053655:Receptors, Interleukin-21 / Q000276:immunology*; D015398:Signal Transduction
D010446:Peptide Fragments; D053655:Receptors, Interleukin-21; C069261:interferon gamma (1-39); D007371:Interferon-gamma