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

Burel, Julie G., Apte, Simon H., Groves, Penny L., McCarthy, James S., and Doolan, Denise L. (2017) Polyfunctional and IFN-γ monofunctional human CD4+ T cell populations are molecularly distinct. JCI Insight, 2 (3). pp. 1-12.

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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.

Item ID: 50070
Item Type: Article (Refereed Research - C1)
ISSN: 2379-3708
Funders: National Health and Medical Research Council (NHMRC), University of Queensland, Queensland Government
Projects and Grants: NHMRC Project grant 1037304
Date Deposited: 05 Sep 2017 02:13
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1117 Public Health and Health Services > 111716 Preventive Medicine @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110704 Cellular Immunology @ 25%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110705 Humoural Immunology and Immunochemistry @ 25%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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