Journal of Autoimmunity (1995) 8, 209–220 Di fferences in Adhesion Markers, Activation Markers, and TcR in Islet Infiltrating vs. Peripheral Lymphocytes in the NOD Mouse Ananda W. Goldrath, Leanne Barber, Karen E. Chen, and Susan E. Alters Applied Immune Sciences, Santa Clara, CA 95054, USA ( Received 12 September 1994 and accepted 2 November 1994) 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  cells. This destruction is characterized 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 destruction we isolated lymphocytes from the islets of prediabetic NOD mice and conducted a comparative phenotypic analysis with the analogous subpopulations of lymphocytes isolated from peripheral blood and lymph node (LN) of the same mice. CD3 + cells were analysed for T cell receptor (TcR); cell bearing  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 activation markers (CD25, CD69) and adhesion markers (CD51, CD54, CD11b, CD49e, L-selectin). Significantly increased levels of CD4 + CD8 + double-positive and CD4  CD8  double-negative T cell popu- lations were observed in the infiltrating lymphocytes as compared with peripheral lymphocytes. In addition, within both CD4 and CD8 sub- populations isolated 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 significantly higher in the periphery for both CD4 + and CD8 + cells than for infiltrating cells. These data describe the phenotype of islet reactive T cells in the NOD mouse and identify possible targets for therapeutic intervention. Correspondence should be addressed to: S. E. Alters, Applied Immune Sciences, 5301 Patrick Henry Drive, Santa Clara, CA 95054, USA. 209 0896-8411/95/020209+12 $08.00/0  1995 Academic Press Limited