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

Publié dans: Blood, 2008, 111 (10), pp.5008-16. ⟨10.1182/blood-2007-11-122259⟩

Auteurs: 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

Résumé

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-gamma (IFN-gamma) and for their cytotoxic response. In patients with IL12RB1 mutations that lead to a complete IL-12Rbeta1 deficiency, the size of this naturally reactive NK cell subset is diminished, in particular for the IFN-gamma 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-12Rbeta1- 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.

Lien vers Pubmed [PMID] – 18319400

Lien vers HAL – hal-00294181

Lien vers le DOI – 10.1182/blood-2007-11-122259