INDUCTION OF INSULITIS IN ATHYMIC (NUDE) MICE - THE EFFECT OF NOD THYMUS AND PANCREAS TRANSPLANTATION

The NOD mouse is a model for human insulin-dependent diabetes mellitus . The disease is thought to have an autoimmune etiology because it is T-cell dependent and is characterized by mononuclear cell infiltration in and around the pancreatic islets of Langerhans. The mechanism by w hich autoreactive T-cells are generated is not fully understood, but i t has been postulated that there is a breakdown in self-tolerance indu ction during intrathymic T-cell maturation, The aim of these studies w as to determine whether transplantation of NOD thymus into diabetes-re sistant mouse strains would generate islet-reactive T-cells. Neonatal thymus was pretreated either by irradiation or culture in 2-deoxyguano sine (dGua) and then transplanted into athymic BALB/c, CBA, and C57BL/ 6 nude mice, Generally, insulitis was not seen in the CBA or C57BL/6 r ecipients, but was found in 56% of BALB/c mice transplanted with an ir radiated NOD thymus and in 46% BALB/c mice with a dGua-treated thymus, Similar experiments in which a NOD fetal pancreas was transplanted in to nude BALB/c mice before NOD thymus transplantation showed a similar frequency and severity of insulitis in both the host pancreas and gra fted NOD pancreas, This suggests that NOD islets are no more prone tha n the host islets to autoimmune attack and do not exacerbate insulitis , Overall, the data suggest that a defect of thymic origin (and correl ating with the thymic epithelium) in the NOD mouse can lead to the dev elopment of autoreactive T-cells and specific islet cell damage. Autor eactivity appears to be restricted to the H-2K(d) allele that is share d by NOD and BALB/c mice,