Level of major histocompatibility complex class I expression on endothelium in non-obese diabetic mice influences CD8 T cell adhesion and migration.
An important prerequisite for development of insulitis and beta-cell destruction in type 1 diabetes is successful transmigration of autoreactive T cells across the islet endothelium. Previous work suggests that antigen presentation to T cells by endothelium, which requires endothelial cell expression of major histocompatibility complex (MHC) molecules, promotes tissue-specific T cell migration. We therefore tested the hypothesis that the level of endothelial MHC class I molecule expression in diabetes-prone mice directly influences autoreactive CD8 T cell migration. We investigated the immune phenotype of endothelial cells, focusing on endothelial MHC class I molecule expression in a range of different tissues and mouse strains, including non-obese diabetic (NOD) mice. In addition, we examined whether the level of expression of MHC class I molecules influences autoantigen-driven CD8 T cell transmigration. Using endothelial cell lines that expressed 'high' (NOD mouse), medium (NOD x C3H/HeJ F(1) generation mice) and no (C3H/HeJ) H-2K(d), we demonstrated in vitro that MHC levels have a profound effect on the activation, adhesion and transmigration of pathogenic, islet autoreactive CD8 T cells. The expression level of MHC class I molecules on endothelial tissues has a direct impact upon the efficiency of migration of autoreactive T cells. The immune phenotype of microvascular endothelium in NOD mice may be an additional contributory factor in disease predisposition or development, and similar phenotypes should be sought in human type 1 diabetes.
Lozanoska-Ochser
B
B
Department of Immunobiology, King's College London, UK. biliana.lozanoska-ochser@kcl.ac.uk
Peakman
M
M
D000818:Animals; D018122:B7-1 Antigen / Q000032:analysis; D060890:B7-H1 Antigen; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002448:Cell Adhesion; D002465:Cell Movement; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology; D019040:E-Selectin / Q000032:analysis; D042783:Endothelial Cells / Q000276:immunology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D010455:Peptides / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013045:Species Specificity; D013950:Thymus Gland / Q000276:immunology
D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D019040:E-Selectin; D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D018799:Intercellular Adhesion Molecule-1