A role for interleukin-12/23 in the maturation of human natural killer and CD56+ T cells in vivo.
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.
Guia
Sophie
S
Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Marseille, France.
Cognet
Céline
C
de Beaucoudrey
Ludovic
L
Tessmer
Marlowe S
MS
Jouanguy
Emmanuelle
E
Berger
Claire
C
Filipe-Santos
Orchidée
O
Feinberg
Jacqueline
J
Camcioglu
Yildiz
Y
Levy
Jacob
J
Al Jumaah
Suliman
S
Al-Hajjar
Sami
S
Stephan
Jean-Louis
JL
Fieschi
Claire
C
Abel
Laurent
L
Brossay
Laurent
L
Casanova
Jean-Laurent
JL
Vivier
Eric
E
D000293:Adolescent; D000328:Adult; D019002:CD56 Antigen; D002648:Child; D002675:Child, Preschool; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D018664:Interleukin-12 / Q000502:physiology*; D053762:Interleukin-12 Subunit p40 / Q000172:deficiency; D053759:Interleukin-23 / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D009154:Mutation; D009164:Mycobacterium Infections / Q000276:immunology; D053707:Receptors, Interleukin-12 / Q000172:deficiency / Q000235:genetics; D012480:Salmonella Infections / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D019002:CD56 Antigen; D053762:Interleukin-12 Subunit p40; D053759:Interleukin-23; D053707:Receptors, Interleukin-12; D018664:Interleukin-12