Lethal NK-mediated inflammation induced by IL-12 in the absence of polymorphic and nonpolymorphic MHC class I molecules.
Cytokine
; 64(1): 25-9, 2013 Oct.
Article
en En
| MEDLINE
| ID: mdl-23891392
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 (ß2M(-/-)) 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 ß2M(-/-) mice, leading to necrosis and eventual death. IL-12/αIL-4 treatment of ß2M(-/-) 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 ß2M 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 ß2M(-/-) mice.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Asesinas Naturales
/
Antígenos de Histocompatibilidad Clase I
/
Microglobulina beta-2
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Interleucina-12
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Subunidad alfa del Receptor de Interleucina-4
/
Inflamación
Límite:
Animals
Idioma:
En
Revista:
Cytokine
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos