ABSTRACT
The destruction of beta cells by the islet infiltrating lymphocytes causes type 1 diabetes. Transgenic mice models expressing interferon (IFN)-beta in beta cells, in the non-obese diabetic (NOD) strain and in a diabetes-free, major histocompatibility complex-matched, homologous strain, the non-obese resistant (NOR) mice, developed accelerated type 1 diabetes after 3 weeks of age. Our aim was to determine if natural killer (NK) cells could affect the acceleration of the disease. We determined the amount of NK cells in the pancreas, spleen and lymph nodes from NOD rat insulin promoter (RIP)-IFN-beta mice. Pancreatic cytokines were assessed by quantitative real-time polymerase chain reaction and protein arrays. To confirm the relevance of NK cells in the acceleration of autoimmune diabetes this subset was depleted with anti-asialo GM1 antibodies. An increase of intrapancreatic NK cells characterized the accelerated onset of diabetes both in NOD and NOR RIP-IFN-beta transgenic models. Cytokines involved in NK function and migration were found to be hyperexpressed in the pancreas from accelerated diabetic mice. Interestingly, the depletion of NK cells in vivo abolished completely the acceleration of diabetes. NK cells connect innate to adaptive immunity and might play a role in autoimmunity. We report here that NK cells are required critically in the pancreas for accelerated diabetes. This model links inflammation to acceleration of beta cell-specific autoimmunity mediated by NK cells.
Subject(s)
Diabetes Mellitus, Type 1/immunology , Interferon-beta/immunology , Killer Cells, Natural/immunology , Animals , B-Lymphocytes/immunology , Cytokines/metabolism , Disease Models, Animal , Disease Progression , G(M1) Ganglioside/immunology , Islets of Langerhans/immunology , Lymph Nodes/immunology , Lymphocyte Subsets/immunology , Mice , Mice, Inbred NODABSTRACT
Gran parte de lo que sabemos sobre el desarrollo de la diabetes mellitus tipo 1 (T1D), se lo debemos a los estudios realizados en el ratón NOD, actualmente uno de los mejores modelos experimentales de esta enfermedad. Estudios realizados en esta cepa murina han demostrado que los linfocitos T son los principales efectores de la destrucción de las células beta pancreáticas. Sin embargo, también se ha observado que otras células del sistema inmune están implicadas en el desarrollo de la enfermedad. Entre ellas, las células dendríticas, los macrófagos y los linfocitos B, son imprescindibles tanto en el inicio como en fases mas avanzadas de la enfermedad. El objetivo de la presente revisión es sintetizar los recientes conocimientos sobre el papel de estas poblaciones celulares como células efectoras en el desarrollo de la T1D (AU)
