Transgenic mice carrying the rearranged T cell receptor of a diabetogenic T cell clone

Abstract

Insulin-dependent diabetes mellitus (IDDM) is a progressive autoimmune disease that results in destruction of the insulin-producing beta cells in the pancreatic islets of langerhans (reviewed in Castano and Eisenbarth, 1990). The genetic and environmental factors which provoke this disease in humans remain largely unknown. Fortunately, the nonobese diabetic (NOD) mouse develops a spontaneous diabetes remarkably similar to that in humans and has thus greatly facilitated its study (Makino et al, 1980). The disease of NOD mice parallels that of the human in that it first develops as an occult infiltration of lymphocytes into the islets, a process termed insulitis, followed by the destruction of the overwhelming majority of the beta cells, thereby, percipitating an overt diabetes. Autoimmune diabetes in NOD mice is under polygenic control, with the most important single contributor being the major histocompatibility complex (MHC) - \(H - {2^{{g^7}}}\).