title: Differences in adhesion markers, activation markers, and TcR in islet infiltrating vs. peripheral lymphocytes in the NOD mouse.
abstract: 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 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 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 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 populations were observed in the infiltrating lymphocytes as compared with peripheral lymphocytes. In addition, within both CD4 and CD8 subpopulations 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.
authors.affiliation: Applied Immune Sciences, Santa Clara, CA 95054, USA.
authors.forename: A W
authors.initials: AW
authors.lastname: Goldrath
authors.forename: L
authors.initials: L
authors.lastname: Barber
authors.forename: K E
authors.initials: KE
authors.lastname: Chen
authors.forename: S E
authors.initials: SE
authors.lastname: Alters
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001327:Autoimmune Diseases / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015415:Biomarkers; D015815:Cell Adhesion Molecules / Q000032:analysis*; D002465:Cell Movement; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology; D005260:Female; D007111:Immunity, Cellular; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology*; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000945:Antigens, Differentiation, T-Lymphocyte; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D011948:Receptors, Antigen, T-Cell