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

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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 Plasmodium falciparum (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.

Authors

Julie G. Burel, Simon H. Apte, Penny L. Groves, James S. McCarthy, Denise L. Doolan