Cell-Mediated Immune Reactions against Islets of Langerhans in Diabetes-Prone BB Rats

Abstract

The intact pancreatic islet can be destroyed by antibody-dependent cell-mediated cytotoxicity (ADCC). T cell-mediated cytotoxicity (CMC) might additionally be important in the pathogenesis of IDDM. However, in vitro alterations of islets due to CMC have so far not been demonstrated. For the evaluation of the cytotoxic attack caused by ADCC and CMC against the islets in the development of IDDM we used a BB rat line with a high incidence of the disease (dp BB/OK). Cytotoxicity tests were carried out on autologous and on nonsyngeneic islets with mononuclear spleen cells and serum from non-diabetic BB rats of different ages. The cytotoxic action of the mononuclear cells was quantified by the specific 51Cr-release from the islets after pretreatment with serum. It was found that an anti-islet cytotoxicity appears with a peak incidence between 40 and 60 days of age. The frequency of cytotoxicity in vitro was related to the incidence of diabetes as normally observed in this rat line. Furthermore, it was shown that both autologous, allogeneic and xenogeneic islets can be destroyed by mononuclear spleen cells and serum of dp BB/OK rats.--The frequency and the strength of anti-islet cytotoxicity in vitro were higher in these dp BB/OK animals than in a control group of non-diabetes prone BB/PhiK rats. There was an association between cytotoxic 51Cr-release in the positive assays and a reduction in the hormone content of pancreatic islets.--This report provides evidence of cell-mediated immune damage of islets during the prediabetic state of BB rats suggesting that both CMC and ADCC are involved in islet cell killing.