IL-6 promotes the differentiation of a subset of naive CD8+ T cells into IL-21-producing B helper CD8+ T cells.
IL-6 is known to contribute to the differentiation of CD4+T cells into different subsets of effector T helper cells. Less is known about the potential of IL-6 in regulating CD8+T cell effector function. Here, we identify IL-6 as a master regulator of IL-21 in effector CD8+T cells. IL-6 promotes the differentiation of a subset of naive CD8+T cells that express IL-6R into a unique population of effector CD8+T cells characterized by the production of high levels of IL-21 and low levels of IFN-γ. Similar to CD4+T follicular helper (Tfh) cells, IL-21-producing CD8+T cells generated in the presence of IL-6 directly provide help to B cells to induce isotype switching. CD8+T cell-derived IL-21 contributes to the production of protective virus-specific IgG antibodies during influenza virus infection. Thus, this study reveals the presence of a new mechanism by which IL-6 regulates antibody production during viral infection, and a novel function of effector CD8+T cells in the protection against viruses.
Department of Medicine/Immunobiology Program, University of Vermont, Burlington, VT 05405.
Rui
0000-0003-4427-2158
R
Yang
Center on Aging and Department of Immunology, University of Connecticut School of Medicine, Farmington, CT 06030.
April R
0000-0002-8656-7328
AR
Masters
Department of Medicine/Immunobiology Program, University of Vermont, Burlington, VT 05405.
Karen A
KA
Fortner
Department of Medicine/Immunobiology Program, University of Vermont, Burlington, VT 05405.
Devin P
0000-0002-1958-7433
DP
Champagne
Department of Medicine/Immunobiology Program, University of Vermont, Burlington, VT 05405.
Natalia
0000-0003-4368-0176
N
Yanguas-Casás
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294.
Daniel J
0000-0002-9600-6954
DJ
Silberger
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294.
Casey T
CT
Weaver
Center on Aging and Department of Immunology, University of Connecticut School of Medicine, Farmington, CT 06030.
Laura
0000-0002-5006-3339
L
Haynes
Department of Medicine/Immunobiology Program, University of Vermont, Burlington, VT 05405 mrincon@uvm.edu.
Mercedes
M
Rincon
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D007378:Interleukins / Q000096:biosynthesis*; D016131:Lymphocyte Subsets / Q000378:metabolism; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000098546:Interleukin-21
D007074:Immunoglobulin G; D015850:Interleukin-6; D007378:Interleukins; D050796:STAT3 Transcription Factor; D000098546:Interleukin-21
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