title: IL-27 increases the proliferation and effector functions of human naïve CD8+ T lymphocytes and promotes their development into Tc1 cells.
abstract: IL-27 has been shown to exhibit both pro- and anti-inflammatory properties; it favors mouse naïve CD4(+) T-cell differentiation into Th1 cells to the detriment of Th17 and Th2 skewing and regulates IL-10 and IL-17 production by human CD4(+) T cells. Moreover, IL-27 promotes proliferation and cytotoxic functions of mouse CD8(+) T lymphocytes, but no data are available on human CD8(+) T cells. We investigated the impact of IL-27 on human CD8(+) T cells. In contrast to mouse T cells, the IL-27 receptor (IL-27R), composed of T cell cytokine receptor (TCCR) and gp130, was detected on a greater percentage of human CD8(+) than CD4(+) T cells and these proportions increased upon polyclonal activation. IL-27 induced rapid STAT1 and STAT3 signaling, enhanced STAT1 protein levels, and induced SOCS1 and SOCS3 expression in a STAT1-dependent manner by human CD8(+) T cells. Addition of IL-27 to α-CD3-activated naïve CD8(+) T cells significantly increased T-box transcription factor expression levels, cell proliferation, and IFN-γ and granzyme B production leading to increased CD8(+) T-cell-mediated cytotoxicity. These results demonstrate that IL-27, a rapidly produced cytokine by activated APC, has a profound impact on human naïve CD8(+) T cells, driving them to become highly efficient Tc1 cells.
authors.affiliation: Department of Medicine, Université de Montréal, CRCHUM-Notre-Dame, Pavilion J.A. De Sève, Montreal, QC, Canada.
authors.forename: Raphael
authors.initials: R
authors.lastname: Schneider
authors.forename: Teodora
authors.initials: T
authors.lastname: Yaneva
authors.forename: Diane
authors.initials: D
authors.lastname: Beauseigle
authors.forename: Lama
authors.initials: L
authors.lastname: El-Khoury
authors.forename: Nathalie
authors.initials: N
authors.lastname: Arbour
mesh_terms: D000951:Antigens, Neoplasm / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002352:Carrier Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130 / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D053804:Granzymes / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D050794:STAT1 Transcription Factor / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000276:immunology / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D017252:CD3 Complex; D002352:Carrier Proteins; C494199:IL6ST protein, human; D020381:Interleukin-17; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; D020825:T-Box Domain Proteins; C454440:UBXN11 protein, human; D050822:Cytokine Receptor gp130; D007371:Interferon-gamma; D053804:Granzymes