Anti-inflammatory cytokines directly inhibit innate but not adaptive CD8+ T cell functions

Bailey E. Freeman, Christine Meyer, Mark Slifka

    Research output: Contribution to journalArticle

    13 Citations (Scopus)

    Abstract

    Virus-specific CD8+ T cells provide classical adaptive immunity by responding to cognate peptide antigen, but they may also act in an "innate" capacity by responding directly to cytokine stimulation. Here, we examined regulation of these distinct T cell functions by anti-inflammatory cytokines (interleukin-4 [IL-4], IL-10, and transforming growth factor β [TGF-β]). Innate gamma interferon (IFN-γ) production by CD8+ T cells following exposure to IL-12 plus IL-18, IL-12 plus tumor necrosis factor alpha (TNF-α), or IL-12 plus IL-15 was inhibited by exposure to anti-inflammatory cytokines either before or shortly after stimulation. However, inhibition was not universal, as other activation parameters, including upregulation of CD25 and CD69, remained largely unaltered. In contrast, peptide-specific T cell responses were resistant to inhibition by anti-inflammatory cytokines. This was not due to downregulation of cytokine receptor expression or an inability to signal through cytokine receptors since phosphorylation of STAT proteins remained intact. These results highlight key differences in cytokine-mediated regulation of innate and adaptive T cell functions, which may help balance effective antiviral immune responses while reducing T cell-mediated immunopathology.

    Original languageEnglish (US)
    Pages (from-to)7474-7484
    Number of pages11
    JournalJournal of Virology
    Volume88
    Issue number13
    DOIs
    StatePublished - 2014

    Fingerprint

    cytokines
    Anti-Inflammatory Agents
    T-lymphocytes
    Cytokines
    T-Lymphocytes
    interleukin-12
    Interleukin-12
    Cytokine Receptors
    peptides
    immunopathology
    Peptide T
    interleukin-18
    Interleukin-15
    transforming growth factors
    Interleukin-18
    protein phosphorylation
    Transforming Growth Factors
    Adaptive Immunity
    interleukin-4
    interleukin-10

    ASJC Scopus subject areas

    • Immunology
    • Virology

    Cite this

    Anti-inflammatory cytokines directly inhibit innate but not adaptive CD8+ T cell functions. / Freeman, Bailey E.; Meyer, Christine; Slifka, Mark.

    In: Journal of Virology, Vol. 88, No. 13, 2014, p. 7474-7484.

    Research output: Contribution to journalArticle

    Freeman, Bailey E. ; Meyer, Christine ; Slifka, Mark. / Anti-inflammatory cytokines directly inhibit innate but not adaptive CD8+ T cell functions. In: Journal of Virology. 2014 ; Vol. 88, No. 13. pp. 7474-7484.
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