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Polyfunctional and IFN-γ monofunctional human CD4+ T cell populations are molecularly distinct

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  • Polyfunctional and IFN-γ monofunctional human CD4+ T cell populations are molecularly distinct

    JCI Insight. 2017 Feb 9;2(3):e87499. doi: 10.1172/jci.insight.87499.
    Polyfunctional and IFN-γ monofunctional human CD4+ T cell populations are molecularly distinct.

    Burel JG1, Apte SH2, Groves PL2, McCarthy JS3, Doolan DL4.
    Author information

    Abstract

    Pathogen-specific polyfunctional T cell responses have been associated with favorable clinical outcomes, but it is not known whether molecular differences exist between polyfunctional and monofunctional cytokine-producing T cells. Here, we report that polyfunctional CD4+ T cells induced during Plasmodiumfalciparum (P. falciparum) blood-stage infection in humans have a unique transcriptomic profile compared with IFN-γ monofunctional CD4+ T cells and, thus, are molecularly distinct. The 14-gene signature revealed in P. falciparum-reactive polyfunctional T cells is associated with cytokine signaling and lymphocyte chemotaxis, and systems biology analysis identified IL-27 as an upstream regulator of the polyfunctional gene signature. Importantly, the polyfunctional gene signature is largely conserved in Influenza-reactive polyfunctional CD4+ T cells, suggesting that polyfunctional T cells have core characteristics independent of pathogen specificity. This study provides the first evidence to our knowledge that consistent molecular differences exist between polyfunctional and monofunctional CD4+ T cells.


    PMID: 28194431 DOI: 10.1172/jci.insight.87499
    [PubMed - in process]
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