Natural killer cells are required for accelerated type 1 diabetes driven by interferon-beta.
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.
Alba
A
A
Laboratory of Immunobiology for Research and Application to Diagnosis (LIRAD), Blood and Tissue Bank (BST), Research Institute Germans Trias i Pujol, Badalona, Barcelona, Spain.
Planas
R
R
Clemente
X
X
Carrillo
J
J
Ampudia
R
R
Puertas
M-C
MC
Pastor
X
X
Tolosa
E
E
Pujol-Borrell
R
R
Verdaguer
J
J
Vives-Pi
M
M
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005677:G(M1) Ganglioside / Q000276:immunology; D016899:Interferon-beta / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD
D016207:Cytokines; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D016899:Interferon-beta