RESUMO
The NK1.1 cell surface receptor, which belongs to the NKR-P1 gene cluster, has been bred onto nonobese diabetic (NOD) mice for two purposes. The first was to tag NK and NKT cells for easier experimental identification of those subsets and better analysis of their implication in type 1 diabetes. The second was to produce a congenic strain carrying Idd6, a susceptibility locus that has been repeatedly mapped in the vicinity of the NKR-P1 gene cluster and the NK complex, to explore the impact of this locus upon autoimmune diabetes. NOD.NK1.1 mice express the NK1.1 marker selectively on the surface of their NK and NKT cell subsets. In addition, the mice manifest reduced disease incidence and improved NK and NKT cell performance, as compared with wild-type NOD mice. The association of those two features in the same congenic strain constitutes a strong argument in favor of Idd6 being associated to the NK complex. This could explain at the same time the multiple alterations of innate immunity reported in NOD mice and the fact that disease onset can be readily modified by boosting the innate immune system of the mouse.
Assuntos
Antígenos/biossíntese , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/prevenção & controle , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Camundongos Congênicos/imunologia , Biossíntese de Proteínas , Proteínas , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Animais , Antígenos Ly , Antígenos de Superfície , Biomarcadores/análise , Citotoxicidade Imunológica/genética , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/genética , Feminino , Predisposição Genética para Doença , Lectinas Tipo C , Camundongos , Camundongos Congênicos/genética , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Subfamília B de Receptores Semelhantes a Lectina de Células NK , PrevalênciaRESUMO
alpha-Galactosylceramide (alpha-GalCer) is a glycolipid with potent antitumor properties that binds to CD1d molecules and activates mouse Valpha14 and human Valpha24 NKT cells. Surprisingly, we found that, as early as 90 min after alpha-GalCer injection in vivo, NK cells also displayed considerable signs of activation, including IFN-gamma production and CD69 induction. NK activation was not observed in RAG- or CD1-deficient mice, and it was decreased by pretreatment with anti-IFN-gamma Abs, suggesting that, despite its rapid induction, it was a secondary event that depended on IFN-gamma release by NKT cells. At later time points, B cells and CD8 T cells also began to express CD69. These findings identify a high-speed communication network between the innate and adaptive immune systems in vivo that is initiated upon NKT cell activation. They also suggest that the antitumor effects of alpha-GalCer result from the sequential recruitment of distinct innate and adaptive effector lymphocytes.