DIFFERENCES IN ADHESION MARKERS, ACTIVATION MARKERS, AND TCR IN ISLETINFILTRATING VS PERIPHERAL LYMPHOCYTES IN THE NOD MOUSE

Insulin dependent diabetes mellitus (IDDM) in the non-obese diabetic ( NOD) mouse is the result of a cellular mediated autoimmune event that destroys pancreatic islet beta cells. This destruction is characterize d by a progressive lymphocytic infiltration into the islets as well as circulating autoantibodies and T cells reactive with islet antigens. To gain a better understanding of the cells responsible for islet dest ruction we isolated lymphocytes from the islets of prediabetic NOD mic e and conducted a comparative phenotypic analysis with the analogous s ubpopulations of lymphocytes isolated from peripheral blood and lymph node (LN) of the same mice. CD3(+) cells were analysed for T cell rece ptor (TcR); cell bearing gamma delta TcR were consistently observed at a higher frequency in the infiltrating T cells than in the periphery. Lymphocytes were also characterized for the expression of CD4 and CD8 T cell markers and, within each population, for the expression of act ivation markers (CD25, CD69) and adhesion markers (CD51, CD54, CD11b, CD49e, L-selectin). Significantly increased levels of CD4(+)CD8(+) dou ble-positive and CD4(-)CD8(-) double-negative T cell populations were observed in the infiltrating lymphocytes as compared with peripheral l ymphocytes. In addition, within both CD4 and CD8 subpopulations isolat ed from islet infiltrates, CD11b(+) and CD49e(+) cells were increased with respect to the same subset of cells isolated from the periphery. In contrast, the level of cells that expressed L-selectin was signific antly higher in the periphery for both CD4(+) and CD8(+) cells than fo r infiltrating cells. These data describe the phenotype of islet react ive T cells in the NOD mouse and identify possible targets for therape utic intervention.