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


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-? 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.

SUBMITTER: Burel JG 

PROVIDER: S-EPMC5291737 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Polyfunctional and IFN-<b>γ</b> monofunctional human CD4<sup>+</sup> T cell populations are molecularly distinct.

Burel Julie G JG   Apte Simon H SH   Groves Penny L PL   McCarthy James S JS   Doolan Denise L DL  

JCI insight 20170209 3


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<sup>+</sup> T cells induced during <i>Plasmodium</i><i>falciparum</i> (<i>P</i>. <i>falciparum</i>) blood-stage infection in humans have a unique transcriptomic profile compared with IFN-γ monofunctional CD4<sup>+</sup> T cells a  ...[more]

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