IL-21 Is Required to Control Chronic Viral Infection
- 19 June 2009
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 324 (5934), 1569-1572
- https://doi.org/10.1126/science.1174182
Abstract
Controlling Chronic Viral Infections: Chronic viral infections such as HIV and hepatitis B and C viruses are major public health concerns. T cell—mediated immune responses are critical for controlling viral infections. In contrast to acute infections, chronic viral infections are characterized by “exhausted” cytotoxic CD8 + T cells, cells which exhibit reduced proliferative capacity, cytokine secretion, and cytotoxicity. Treatments that reverse exhaustion result in increased viral control. Despite their exhaustion, these CD8 + T cells eventually help to control chronic infections by killing virally infected cells, and require CD4 + T cell help to do so. How do CD4 + T cells provide help to CD8 + T cells during chronic infection (see the Perspective by Johnson and Jameson )? Elsaesser et al. (p. 1569 , published online 7 May), Yi et al. (p. 1572 , published online 14 May), and Fröhlich et al. (p. 1576 , published online 28 May) now show that the cytokine, interleukin-21 (IL-21), known to be critical for the differentiation of certain CD4 + T cell effector subsets, is an essential factor produced by CD4 + T cells that helps CD8 + T cells to control chronic lymphocytic choriomeningitis virus infection in mice. Acute and chronic infections resulted in differing amounts of IL-21 production by virus-specific CD4 + T cells. CD8 + T cells required IL-21 directly, and when CD8 + T cells were unable to signal through IL-21 or IL-21 was not available, they were reduced in number, exhibited a more exhausted phenotype, and were not able to control the virus. In contrast, the absence of IL-21–dependent signaling did not affect primary CD8 + T cell responses to acute infection or responses to a viral rechallenge, suggesting that differentiation of memory CD8 + T cells is independent of IL-21.Keywords
This publication has 20 references indexed in Scilit:
- Interleukin-21: Basic Biology and Implications for Cancer and AutoimmunityAnnual Review of Immunology, 2008
- Spontaneous Recovery in Acute Human Hepatitis C Virus Infection: Functional T-Cell Thresholds and Relative Importance of CD4 HelpJournal of Virology, 2008
- Interleukin-10 determines viral clearance or persistence in vivoNature Medicine, 2006
- Resolution of a chronic viral infection after interleukin-10 receptor blockadeThe Journal of Experimental Medicine, 2006
- Restoring function in exhausted CD8 T cells during chronic viral infectionNature, 2005
- T cells and viral persistence: lessons from diverse infectionsNature Immunology, 2005
- Intrinsic Functional Dysregulation of CD4 T Cells Occurs Rapidly following Persistent Viral InfectionJournal of Virology, 2005
- HCV Persistence and Immune Evasion in the Absence of Memory T Cell HelpScience, 2003
- A Critical Role for IL-21 in Regulating Immunoglobulin ProductionScience, 2002
- Selection of genetic variants of lymphocytic choriomeningitis virus in spleens of persistently infected mice. Role in suppression of cytotoxic T lymphocyte response and viral persistence.The Journal of Experimental Medicine, 1984