title: A Critical Role of IL-21-Induced BATF in Sustaining CD8-T-Cell-Mediated Chronic Viral Control.
abstract: Control of chronic viral infections by CD8 T cells is critically dependent on CD4 help. In particular, helper-derived IL-21 plays a key role in sustaining the CD8 T cell response; however, the molecular pathways by which IL-21 sustains CD8 T cell immunity remain unclear. We demonstrate that IL-21 causes a phenotypic switch of transcription factor expression in CD8 T cells during chronic viral infection characterized by sustained BATF expression. Importantly, BATF expression during chronic infection is both required for optimal CD8 T cell persistence and anti-viral effector function and sufficient to rescue "unhelped" CD8 T cells. Mechanistically, BATF sustains the response by cooperating with IRF4, an antigen-induced transcription factor that is also critically required for CD8 T cell maintenance, to preserve Blimp-1 expression and thereby sustain CD8 T cell effector function. Collectively, these data suggest that CD4 T cells "help" the CD8 response during chronic infection via IL-21-induced BATF expression.
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, 8727 West Watertown Plank Road, Milwaukee, WI 53213, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Xin
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, 8727 West Watertown Plank Road, Milwaukee, WI 53213, USA; Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, 8701 West Watertown Plank Road, Milwaukee, WI 53226, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Schauder
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Begoña
authors.initials: B
authors.lastname: Lainez
authors.affiliation: Department of Medicine, Yale University School of Medicine, New Haven, CT 06520. USA.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Weinstein
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, 8727 West Watertown Plank Road, Milwaukee, WI 53213, USA.
authors.forename: Zhengxi
authors.initials: Z
authors.lastname: Dai
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, 8727 West Watertown Plank Road, Milwaukee, WI 53213, USA.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Enric
authors.initials: E
authors.lastname: Esplugues
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, 8727 West Watertown Plank Road, Milwaukee, WI 53213, USA.
authors.forename: Renren
authors.initials: R
authors.lastname: Wen
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, 8727 West Watertown Plank Road, Milwaukee, WI 53213, USA.
authors.forename: Demin
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Immunology and Infectious Disease, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Parish
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, 845 19(th) Street South, Birmingham, AL 35294, USA.
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Zajac
authors.affiliation: Department of Medicine, Yale University School of Medicine, New Haven, CT 06520. USA.
authors.forename: Joe
authors.initials: J
authors.lastname: Craft
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, 8727 West Watertown Plank Road, Milwaukee, WI 53213, USA; Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, 8701 West Watertown Plank Road, Milwaukee, WI 53226, USA. Electronic address: weiguo.cui@bcw.edu.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Cui
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D050835:Interferon Regulatory Factors / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D000074462:Positive Regulatory Domain I-Binding Factor 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014777:Virus Diseases / Q000276:immunology*; D000098546:Interleukin-21; D000099218:Interferon Regulatory Factor-4
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D050835:Interferon Regulatory Factors; D007378:Interleukins; D000074462:Positive Regulatory Domain I-Binding Factor 1; D014157:Transcription Factors; D000098546:Interleukin-21; D000099218:Interferon Regulatory Factor-4; C431772:Batf protein, mouse; C513258:Prdm1 protein, mouse
keywords: BATF; Blimp-1; CD8 T cell; IL-21; IRF4; LCMV; STAT3