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.