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Accelerated Type 1 Diabetes Induction in Mice by Adoptive Transfer of Diabetogenic CD4+ T Cells
Published on: May 6, 2013
Natural killer cells are required for accelerated type 1 diabetes driven by interferon-beta
1Laboratory of Immunobiology for Research and Application to Diagnosis (LIRAD), Blood and Tissue Bank (BST), Research Institute Germans Trias i Pujol, Badalona, Barcelona, Spain.
Clinical and Experimental Immunology
|January 15, 2008
Summary
Natural killer (NK) cells accelerate type 1 diabetes by infiltrating the pancreas. Depleting NK cells prevented accelerated diabetes, revealing their critical role in this autoimmune disease.
Area of Science:
- Immunology
- Endocrinology
- Autoimmunity
Background:
- Type 1 diabetes results from beta cell destruction by immune cells.
- Interferon-beta (IFN-beta) expression in beta cells accelerates type 1 diabetes in transgenic mouse models.
- The role of natural killer (NK) cells in this accelerated autoimmune process is not fully understood.
Purpose of the Study:
- To investigate the impact of natural killer (NK) cells on the acceleration of type 1 diabetes in IFN-beta transgenic mice.
- To determine if NK cells are critical for the accelerated onset of autoimmune diabetes.
Main Methods:
- Quantified NK cell populations in the pancreas, spleen, and lymph nodes of NOD and NOR RIP-IFN-beta transgenic mice.
- Assessed pancreatic cytokine expression using quantitative real-time polymerase chain reaction and protein arrays.
- Depleted NK cells in vivo using anti-asialo GM1 antibodies to assess their role in diabetes acceleration.
Main Results:
- An increased number of intrapancreatic NK cells correlated with accelerated diabetes onset in both NOD and NOR RIP-IFN-beta models.
- Hyperexpression of cytokines involved in NK cell function and migration was observed in the pancreas of accelerated diabetic mice.
- Complete depletion of NK cells abolished the acceleration of diabetes.
Conclusions:
- NK cells are critically required in the pancreas for the acceleration of autoimmune diabetes.
- This study establishes a link between pancreatic inflammation, NK cell activity, and the acceleration of beta cell-specific autoimmunity.
- NK cells may serve as a crucial link between innate and adaptive immunity in the development of autoimmune diabetes.
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