IL-21 is required to control chronic viral infection.
CD4+ and CD8+ T cell functions are rapidly aborted during chronic infection, preventing viral clearance. CD4+ T cell help is required throughout chronic infection so as to sustain CD8+ T cell responses; however, the necessary factor(s) provided by CD4+ T cells are currently unknown. Using a mouse model of chronic viral infection, we demonstrated that interleukin-21 (IL-21) is an essential component of CD4+ T cell help. In the absence of IL-21 signaling, despite elevated CD4+ T cell responses, CD8+ T cell responses are severely impaired. CD8+ T cells directly require IL-21 to avoid deletion, maintain immunity, and resolve persistent infection. Thus, IL-21 specifically sustains CD8+ T cell effector activity and provides a mechanism of CD4+ T cell help during chronic viral infection.
Elsaesser
Heidi
H
Department of Microbiology, Immunology, and Molecular Genetics and University of California, Los Angeles (UCLA) AIDS Institute, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA.
Sauer
Karsten
K
Brooks
David G
DG
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction; D014777:Virus Diseases / Q000276:immunology*; D000098546:Interleukin-21
D007378:Interleukins; D000098546:Interleukin-21