A role for interleukin-12/23 in the maturation of human natural killer and CD56+ T cells in vivo

Sophie Guia, Céline Cognet, Ludovic De Beaucoudrey, Marlowe S. Tessmer, Emmanuelle Jouanguy, Claire Berger, Orchidée Filipe-Santos, Jacqueline Feinberg, Yildiz Camcioglu, Jacob Levy, Suliman Al Jumaah, Sami Al-Hajjar, Jean Louis Stephan, Claire Fieschi, Laurent Abel, Laurent Brossay, Jean Laurent Casanova, Eric Vivier

    Research output: Contribution to journalArticlepeer-review

    52 Scopus citations

    Abstract

    Natural killer (NK) cells have been originally defined by their "naturally occurring" effector function. However, only a fraction of human NK cells is reactive toward a panel of prototypical tumor cell targets in vitro, both for the production of interferon-γ (IFN-γ) and fortheir cytotoxic response. In patients with IL12RB1 mutations that lead to a complete IL-12R(β1 deficiency, the size of this naturally reactive NK cell subset is diminished, in particular for the IFN-γ production. Similar data were obtained from a patient with a complete deficit in IL-12p40. In addition, the size of the subset of effector memory T cells expressing CD56 was severely decreased in IL-12Rβ1-and IL-12p40-deficient patients. Human NK cells thus require in vivo priming with IL-12/23 to acquire their full spectrum of functional reactivity, while T cells are dependent upon IL-12/23 signals for the differentiation and/or the maintenance of CD56+ effector memory T cells. The susceptibility of IL-12/23 axis-deficient patients to Mycobacterium and Salmonella infections in combination with the absence of mycobacteriosis or salmonellosis in the rare cases of human NK cell deficiencies point to a role for CD56+ T cells in the control of these infections in humans.

    Original languageEnglish
    Pages (from-to)5008-5016
    Number of pages9
    JournalBlood
    Volume111
    Issue number10
    DOIs
    StatePublished - 15 May 2008

    ASJC Scopus subject areas

    • Biochemistry
    • Immunology
    • Hematology
    • Cell Biology

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