Diabetes Research Center (DRC)
Washington University in St. Louis

Dana R. Abendschein, Ph.D.

Mary Markiewicz, Ph.D.

Research Assistant Professor

Pathology and Immunology

Mailing Address   Campus box 8118
660 S. Euclid Ave
St. Louis, MO 63119
Office Location   CSRB 7721
Office: Phone:   (314) 747-0816
Lab Phone:   (314) 362-4609
Fax:   (314) 362-8888
E-mail address:   mmarkie@pathology.wustl.edu

Research Interest:

Complications

Islet Biology and Immunology

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Category(ies) of Research:

Basic

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Descriptor of Research:

The expression of NKG2D ligands on -islet cells of the pancreas is proposed to play a key role in the pathogenesis of Type 1 diabetes . Data generated with the non-obese diabetic (NOD) mouse model suggest this may be via engagement of NKG2D on cytotoxic T cells (CTLs) with RAE1 expressed on islet cells. However, how NKG2D could function in this setting is not clear. To directly address the function of NKG2D on CTLs in the development of diabetes, we generated a transgenic mouse that expresses the NKG2D ligand RAE1 in -islet cells of the pancreas. Our preliminary data show that adoptively transferred CTLs are recruited to the pancreatic islets of these mice via NKG2D engagement. This resulted in the subsequent recruitment of additional lymphocytes to the islets. This is consistent with a mild, spontaneous insulitis that was we also observed in older, unmanipulated RAE1 transgenic mice. However no mice developed diabetes. These results suggest that RAE1 may be involved in recruiting immune cells to the pancreas, but that other additional factors, most likely islet-specific T cells, are required to induce diabetes. Therefore, we now plan to turn to models in which mice develop overt diabetes to investigate the roles of NKG2D and RAE1 on CTL-mediated islet destruction.

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Dept. of Pathology & Immunology

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PubMed