Authors: Lozanoska-Ochser, B.; Peakman, M.

Source: Clinical & Experimental Immunology, Volume 157, Number 1, July 2009 , pp. 119-127(9)

Publisher: Wiley-Blackwell

Abstract:

Summary

An important prerequisite for development of insulitis and β-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 × C3H/HeJ F₁ 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.

Keywords: endothelial cells; CD8 T cells; migration; NOD mouse; trafficking

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2249.2009.03940.x

Publication date: 2009-07-01

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