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

作者：Guia Sophie; Cognet Celine; de Beaucoudrey Ludovic; Tessmer Marlowe S; Jouanguy Emmanuelle; Berger Claire; Filipe Santos Orchidee; Feinberg Jacqueline; Camcioglu Yildiz; Levy Jacob; Al Jumaah Suliman; Al Hajjar Sami; Stephan Jean Louis; Fieschi Claire; Abel Laurent; Brossay Laurent; Casanova Jean Laurent; Vivier Eric^*

来源：Blood, 2008, 111(10): 5008-5016.

DOI：10.1182/blood-2007-11-122259

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-12R beta 1 deficiency, the size of this naturally reactive NK cell subset is diminished, in particular for the IFN-gamma production. Similardata 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-12R beta 1- 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.

• 出版日期2008-5-15