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Immunomodulation and cytokine profiling in type 1 diabetes

Friday 18 February 2011

Project
Type 1 diabetes is an autoimmune disease characterized by the selective destruction of the insulin-producing beta cells in the pancreas. A key role in this process is played by T cells.

After clinical onset of the disease a substantial part of the patients experience a honeymoon period, in which there is a very low insulin requirement and good metabolic control. This honeymoon period does not develop in all patients and can be of variable duration.

The initial trigger, leading to the immunological cascade ultimately ending in the clinical onset of type 1 diabetes is not known. Heat Shock Protein 60 (HSP60) is naturally expressed upon stress and therefore present at sites of inflammation. Also, a immunoregulatory role for HSP60 has been reported in various diseases, among which type 1 diabetes.

HSP60 peptides can be are recognized in recently onset type 1 diabetes patients and may be used therapeutically to induce a more tolerogenic environment, ameliorating the progression of the disease.

We set out to establish a cohort of newly diagnosed type 1 diabetes patients, which will be followed over time to evaluate T cell functions and recognition of specific HSP peptides.

The cohort will also be used for cytokine profiling. A possible relation between progression of the disease, metabolic control and cytokine profiles will be investigated.

We will try to determine whether a honeymoon phase is correlated with recognition of HSP peptides and with a specific protective cytokine profile.

Techniques
Cell culture of T cells and different types of DC, FACS, Elisa, luminex, gel electrophoresis, confocal microscopy, immunohistochemistry, in vivo animal studies

Duration
6 or 9 months

Contact
Dr. Mark Klein, 088 75 555 55 (pager 4118), mklein01@umcutrecht.nl