The absence of CD62L (L-selectin) does not inhibit the progression of autoimmune diabetes in nonobese diabetic (NOD) mice

Insulin dependent diabetes mellitus (IDDM) results from an autoreactive immune response targeting the insulin producing β cells found in the islets of Langerhans in the pancreas. Diabetogenesis depends on β cell-reactive T cells trafficking to the islets of Langerhans and effecting β cell destruction. The nonobese diabetic (NOD) mouse spontaneously develops autoimmune diabetes and serves as an excellent model for investigating the immunological processes involved in β cell autoimmunity.; Leukocyte trafficking relies on distinct families of adhesion molecules that regulate tissue-specific homing to secondary lymphoid organs and sites of inflammation. Extravasation begins with the rolling of leukocytes along the endothelial wall and occurs through leukocyte-endothelial cell interactions mediated by the selectin family. One member of the selectin family, CD62L (L selectin), is expressed on virtually all leukocytes and is critical for the efficient population of peripheral lymph nodes, homing to inflamed tissues, and the generation of primary T cell responses.; We and others have previously shown that administration of monoclonal antibodies directed against CD62L can reduce insulitis and prevent diabetes in NOD mice. Prevention is most effective when treatment is begun at an early age, suggesting a crucial role for CD62L in the initial recruitment of T cells to the pancreas and establishment of insulitis.; To further examine the role of CD62L in the development of IDDM, NOD mice with a disrupted CD62L gene were established. The lack of CD62L had no apparent effect on the time of onset or frequency of diabetes. Furthermore, T cell activation, homing, and β cell-specific reactivity in CD62L −/− mice were similar to CD62L+/+ mice. We also evaluated the importance of CD62L in a CD4+ transgenic T cell adoptive transfer model of diabetes. No discernible difference in homing to the pancreatic lymph nodes or induction of diabetes was observed in the absence of CD62L. We conclude that CD62L is not absolutely required for the development of IDDM in NOD mice.