IL-21-Induced MHC Class II+ NK Cells Promote the Expansion of Human Uncommitted CD4+ Central Memory T Cells in a Macrophage Migration Inhibitory Factor-Dependent Manner.
Fiche publication
Date publication
juillet 2016
Journal
Journal of immunology (Baltimore, Md. : 1950)
Auteurs
Membres identifiés du Cancéropôle Est :
Pr ADOTEVI Olivier, Pr BORG Christophe, Dr FERRAND Christophe, Dr GODET Yann, Dr GALAINE Jeanne, Dr LOYON Romain
Tous les auteurs :
Loyon R, Picard E, Mauvais O, Queiroz L, Mougey V, Pallandre JR, Galaine J, Mercier-Letondal P, Kellerman G, Chaput N, Wijdenes J, Adotévi O, Ferrand C, Romero P, Godet Y, Borg C
Lien Pubmed
Résumé
NK cells are critical for innate immunity-mediated protection. The main roles of NK cells rely on their cytotoxic functions or depend on the tuning of Th1 adaptive immunity by IFN-γ. However, the precise influence of inflammatory cytokines on NK cell and CD4 T lymphocyte interactions was never investigated. In this study, we provide evidence that IL-21, a cytokine produced during chronic inflammation or infectious diseases, promotes the differentiation of a specific subset of NK cells coexpressing CD86 and HLA-DR and lacking NKp44. More importantly, IL-21-propagated HLA-DR(+) NK cells produce macrophage migration inhibitory factor and provide costimulatory signaling during naive CD4(+) T cell priming inducing the differentiation of uncommitted central memory T cells. Central memory T cells expanded in the presence of HLA-DR(+) NK cells are CXCR3(+)CCR6(-)CCR4(-)CXCR5(-) and produce IL-2, as well as low levels of TNF-α. Costimulation of CD4(+) T cells by HLA-DR(+) NK cells prevents the acquisition of effector memory phenotype induced by IL-2. Moreover, we identified this population of NK HLA-DR(+) macrophage migration inhibitory factor(+) cells in inflammatory human appendix. Collectively, these results demonstrate a novel function for IL-21 in tuning NK and CD4(+) T cell interactions promoting a specific expansion of central memory lymphocytes.
Mots clés
B7-2 Antigen, metabolism, Cell Communication, Cell Differentiation, Cell Proliferation, Cells, Cultured, Cytokines, metabolism, Cytotoxicity, Immunologic, HLA-DR Antigens, metabolism, Humans, Immunity, Innate, Immunologic Memory, Inflammation, immunology, Interleukins, metabolism, Intramolecular Oxidoreductases, metabolism, Killer Cells, Natural, immunology, Macrophage Migration-Inhibitory Factors, metabolism, Macrophages, immunology, Th1 Cells, immunology, Tonsillitis, immunology
Référence
J. Immunol.. 2016 Jul;197(1):85-96