There is growing evidence that memory T cells are associated with a variety of autoimmune conditions, including type 1 diabetes (T1D). While autoreactive T cells are detected in both patients and healthy control subjects, CD45RO+ memory autoreactive T cells are usually found in patients but not in controls. Our own studies in several pancreas transplant recipients with T1D recurrence have shown that autoreactive memory T cells can be found in the circulation and pancreas transplant lymph nodes. Moreover, the examination of pancreas transplant biopsies from two of such patients shows that most (~80%) of the islet infiltrating T cells have a memory phenotype. Based on this findings we hypothesize that memory cells should be present in the islet infiltrates of nPOD patients. Specifically, we plan to study pancreatic tissue obtained from patients with proven insulits for the presence of the T cells bearing the memory marker CD45RO. It is plausible that the frequency of the memory cells may be related to disease duration, and perhaps this could be higher in the lesions of patients with longer disease duration who still have insulitis. It is also possible that there will be a difference compared to pancreas transplant recipients with recurrent disease. Understanding whether memory T cells represent a significant component of islet infiltrating T cells is relevant to a more complete characterization of the insulitis. A recent clinical trial in new onset patients has tested Alefacept, an anti-memory T cell drug. Demonstrating memory T cells in the lesion would provide further rationale for regimens that target memory T cells, with Alefacept or with new drugs that have similar effects. Furthermore, if memory cells are demonstrated, we can propose additional work to better define the memory phenotype by staining for additional markers.