Insulin‐specific T cells are a predominant component of islet infiltrates in pre‐diabetic NOD mice

Abstract

Numerous investigation have demonstrated that T cells are involved in destruction of beta cells in the NOD mouse, a widely studied model of type I diabetes. In this report we describe a series of islet-specific T cell lines established from islet-infiltrating lymphocytes obtained from individual pre-diabetic NOD mice as well as a large panel of clones derived from these lines. Proliferation assays indicated that these nominally islet-specific lines responded vigorously to porcine insulin. Furthermore, of 40 islet-specific clones derived from lines established from 12-week-old mice, 22 (55%) responded to insulin. A similar analysis of islet-specific clones established from 7-week-old mice indicated that 2 of 14 (14%) were insulin specific. These findings demonstrate that insulin-specific T cells can comprise a major portion of the spontaneously arising T cell response to islets in NOD mice.

A cholera toxoid-insulin conjugate as an oral vaccine against spontaneous autoimmune diabetes

“…The observations that overt diabetes is often preceded by autoantibodies reactive to insulin (20) and that islet-infiltrating cells isolated from NOD mice are enriched in insulin-specific T cells (21) suggest that an immune -1,2ϩ (A, B) and Thy-1,1ϩ (C, D). Original magnifications ϫ250.…”

“…The nonobese diabetic (NOD) mouse spontaneously develops an autoimmune disease sharing immunological and histopathological similarities with type I insulin-dependent diabetes mellitus in humans (19)(20)(21)(22). Prolonged feeding of large (milligram) amounts of heterologous insulin has been shown to delay the onset of diabetes in NOD mice (23).…”

Do the peptide-binding properties of diabetogenic class II molecules explain autoreactivity?

“…Insulin, and particularly the 9-23 peptide of the insulin beta chain, is a primary target of T cell reactivity in both the human disease and the NOD mouse [38,39] (in this issue, contribution by Eisenbarth). Initial binding studies of the B:(9-23) peptide to soluble I-A g7 in detergent free conditions revealed poor binding and fast dissociation rates [10,13,14,40].…”

Proinsulin: a unique autoantigen triggering autoimmune diabetes

“…Pathogenic T cells specific for these 2 antigens are present in significant numbers in infiltrated islets of NOD mice (which develop spontaneous IDDM) and exhibit efficient diabetogenic properties, as demonstrated by their capacity to transfer disease to immunoincompetent syngeneic recipients (9)(10)(11)(12)(13). Two different transgenic animal models were analyzed: NOD-PI mice, which overexpress proinsulin 2 in their APCs (14), and NOD-IGRP mice, which overexpress IGRP in their APCs.…”