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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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Cells, Cultured
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Female
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Flow Cytometry
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HEK293 Cells
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Humans
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Immunity, Innate / immunology
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Interleukin-10 / genetics
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Interleukin-10 / immunology*
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Interleukin-10 / metabolism
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Interleukin-17 / genetics
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Interleukin-17 / immunology*
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Interleukin-17 / metabolism
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Interleukin-2 / genetics
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Interleukin-2 / metabolism
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Luminescent Proteins / genetics
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Luminescent Proteins / metabolism
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Orthomyxoviridae Infections / immunology
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Orthomyxoviridae Infections / metabolism
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Orthomyxoviridae Infections / virology
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Positive Regulatory Domain I-Binding Factor 1
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Signal Transduction / immunology
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T-Lymphocytes, Cytotoxic / immunology*
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T-Lymphocytes, Cytotoxic / metabolism
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T-Lymphocytes, Cytotoxic / virology
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T-Lymphocytes, Helper-Inducer / immunology
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T-Lymphocytes, Helper-Inducer / metabolism
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Transcription Factors / genetics
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Transcription Factors / immunology*
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Transcription Factors / metabolism
Substances
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Interleukin-17
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Interleukin-2
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Luminescent Proteins
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Prdm1 protein, mouse
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Transcription Factors
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Interleukin-10
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Positive Regulatory Domain I-Binding Factor 1