Journal
JCI INSIGHT
Volume 2, Issue 3, Pages -Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.87499
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Funding
- Medicines for Malaria Venture
- National Health and Medical Research Council of Australia (NHMRC) [1037304]
- International Research Tuition Award from the University of Queensland
- NHMRC
- Government of Queensland Clinical Research Fellowship
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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-gamma 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.
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