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Publication : Level of major histocompatibility complex class I expression on endothelium in non-obese diabetic mice influences CD8 T cell adhesion and migration.

First Author  Lozanoska-Ochser B Year  2009
Journal  Clin Exp Immunol Volume  157
Issue  1 Pages  119-27
PubMed ID  19659777 Mgi Jnum  J:151306
Mgi Id  MGI:4353534 Doi  10.1111/j.1365-2249.2009.03940.x
Citation  Lozanoska-Ochser B, et al. (2009) Level of major histocompatibility complex class I expression on endothelium in non-obese diabetic mice influences CD8 T cell adhesion and migration. Clin Exp Immunol 157(1):119-27
abstractText  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.
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