Lethal NK-mediated inflammation induced by IL-12 in the absence of polymorphic and nonpolymorphic MHC class I molecules

Abstract

Interleukin-12 is a potent activator and initiator of type-1 T cell development, and can be used as an adjuvant to bias for the development of vaccine-induced Th1 immune responses. During vaccination of MHC class I deficient beta-2 microglobulin knockout mice (β2M−/−) with an IL-12/αIL-4 Th1 biasing procedure, all of the mice died. None of the IL-12/αIL-4 treated wild type mice developed any noticeable complications. We hypothesized that NK cells may be activated by IL-12 treatment in these β2M−/− mice, leading to necrosis and eventual death. IL-12/αIL-4 treatment of β2M−/− mice resulted in increased NK cell numbers and activation status (IFN-γ+, CD69+). Finally, in vivo depletion of NK cells reversed the pathology induced by IL-12/αIL-4 treatment in β2M deficient mice. These results indicate that IL-12 combined with αIL-4 irreversibly activates NK cells leading to a disseminated inflammatory pathology and death in β2M−/− mice.

Chronic infusion of interleukin‐17 promotes hypertension, activation of cytolytic natural killer cells, and vascular dysfunction in pregnant rats

“…IL‐12 activates NK cells and stimulates them to produce IFN‐ γ (Eickhoff et al. ; Lusty et al. ) that is also increased in the placentas of our IL‐17 infusion group (Fig.…”