title: Polyfunctional and IFN-γmonofunctional 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 duringPlasmodiumfalciparum(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 inP.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 inInfluenza-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.affiliation: Molecular Vaccinology Laboratory, QIMR Berghofer Medical Research Institute.|University of Queensland, School of Medicine.
authors.forename: Julie G
authors.initials: JG
authors.lastname: Burel
authors.affiliation: Molecular Vaccinology Laboratory, QIMR Berghofer Medical Research Institute.
authors.forename: Simon H
authors.initials: SH
authors.lastname: Apte
authors.affiliation: Molecular Vaccinology Laboratory, QIMR Berghofer Medical Research Institute.
authors.forename: Penny L
authors.initials: PL
authors.lastname: Groves
authors.affiliation: University of Queensland, School of Medicine.|Clinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: James S
authors.initials: JS
authors.lastname: McCarthy
authors.affiliation: Molecular Vaccinology Laboratory, QIMR Berghofer Medical Research Institute.|University of Queensland, School of Medicine.|Centre for Biosecurity and Tropical Infectious Diseases, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia.
authors.forename: Denise L
authors.initials: DL
authors.lastname: Doolan
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002633:Chemotaxis; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D064094:Interleukin-27 / Q000378:metabolism; D016778:Malaria, Falciparum / Q000097:blood / Q000276:immunology* / Q000469:parasitology; D010963:Plasmodium falciparum / Q000276:immunology*; D059467:Transcriptome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D064094:Interleukin-27; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma