T lymphocytes capable of activating endothelial cells in vitro are present in rats with autoimmune diabetes.
Endothelial activation as evidenced by increased expression of leukocyte adhesion molecules occurs during immune-mediated inflammatory processes. One such process is insulitis, the pancreatic islet inflammation that leads to autoimmune insulin-dependent diabetes mellitus (IDDM). To determine if the induction of IDDM correlates with the presence of T lymphocytes capable of activating endothelial cells (EC), we studied the diabetes resistant BB (DR) rat. These animals become diabetic after in vivo depletion of T cells expressing the RT6 alloantigen. Various populations of purified DR T lymphocytes were cocultured with MHC compatible rat EC. We observed: 1) RT6- T cells from diabetic animals induced maximal endothelial MHC Ag expression. 2) The ability of RT6- T cells to activate EC increased with the duration of in vivo RT6 depletion. It was acquired before the onset of insulitis but subsided after the onset of diabetes. 3) In contrast, neither unsorted total T cells nor in vitro-purified RT6- T cells activated EC. 4) Older DR rats depleted of RT6+ T cells did not become diabetic and their RT6- T cells did not activate EC. 5) T cell IFN-gamma production correlated with the intensity of EC activation. 6) direct T cell-EC contact was required for maximal IFN-gamma production and EC activation. We conclude that RT6- T cells capable of activating EC are generated during the induction of IDDM in DR rats. We hypothesize that such T cell activity may lead to endothelial activation in vivo and contribute to immune-mediated insulitis, beta-cell destruction, and IDDM.
Doukas
J
J
Department of Medicine, University of Massachusetts Medical Center, Worcester 01655.
Mordes
J P
JP
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007371:Interferon-gamma / Q000096:biosynthesis; D051381:Rats; D013601:T-Lymphocytes / Q000502:physiology*
D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma