title: CD4+ T cell help and innate-derived IL-27 induce Blimp-1-dependent IL-10 production by antiviral CTLs.
abstract: Interleukin (IL)-10 is an important regulatory cytokine that can modulate excessive immune mediated injury. Several distinct cell types have been demonstrated to produce IL-10, including most recently CD8+ cytotoxic T lymphocytes (CTLs) responding to respiratory virus infection. Here we report that CD4+ T cell help in the form of IL-2 is required for IL-10 production by CTLs, but not for the induction of CTL effector cytokines. We show that IL-2 derived from CD4+ helper T cells cooperates with innate immune cell-derived IL-27 to amplify IL-10 production by CTLs through a Blimp-1-dependent mechanism. These findings reveal a previously unrecognized pathway that coordinates signals derived from innate and helper T cells to control the production of a regulatory cytokine by CTLs during acute viral infection.
authors.affiliation: The Beirne B. Carter Center for Immunology Research, The University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.forename: Haley
authors.initials: H
authors.lastname: Dodd
authors.forename: Emily K
authors.initials: EK
authors.lastname: Moser
authors.forename: Rahul
authors.initials: R
authors.lastname: Sharma
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Braciale
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000378:metabolism / Q000821:virology; D000074462:Positive Regulatory Domain I-Binding Factor 1; D015398:Signal Transduction / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D007376:Interleukin-2; D008164:Luminescent Proteins; C513258:Prdm1 protein, mouse; D014157:Transcription Factors; D016753:Interleukin-10; D000074462:Positive Regulatory Domain I-Binding Factor 1