title: Transplanted islets from lpr mice are resistant to autoimmune destruction in a model of streptozotocin-induced type I diabetes.
abstract: The mechanism by which beta-cells die during autoimmune diabetes has remained a subject of intense investigation. The loss of beta-cells in the disease is T cell mediated and thought to result from a number of different insults including apoptosis induction through the death receptor CD95. However, the role of CD95 in autoimmune diabetes, studied primarily in the non-obese diabetic (NOD) mouse model, has been controversial. We have used an alternative model of autoimmune diabetes triggered by repeated low doses of streptozotocin. In this model, islet grafts from C3H mice that carry the lpr mutation, and therefore lack the ability to undergo apoptosis through CD95-CD95L interaction, were completely protected when grafted in autoimmune diabetic mice despite periinsulitis (infiltration of T cells) which however did not progress to islet destruction. In contrast wild-type grafts were rapidly eliminated in autoimmune recipients. Our data provide strong support for a major role of CD95 in the destruction of islets in autoimmune mice.
authors.affiliation: The Ben May Institute for Cancer Research, Committees on Immunology and Cancer Biology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: S
authors.initials: S
authors.lastname: Vijayan
authors.forename: P
authors.initials: P
authors.lastname: Zhou
authors.forename: T W
authors.initials: TW
authors.lastname: Rajapaksha
authors.forename: M -L
authors.initials: M-
authors.lastname: Alegre
authors.forename: M E
authors.initials: ME
authors.lastname: Peter
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000473:pathology*; D004195:Disease Models, Animal; D007515:Islets of Langerhans / Q000166:cytology; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D013311:Streptozocin
chemical_list: D013311:Streptozocin