Effect of lymphocytes and serum from probands before and after manifestation of type 1 (insulin-dependent) diabetes on rat islets in vitro.

In a two-year follow-up study neonatal rat islets have been shown to be affected in vitro by lymphocytes and complement-inactivated serum obtained from newly diagnosed Type 1 (insulin-dependent) diabetic patients and probands who are at high risk for developing the disease. The effect was measured by 51Cr-release of the islets treated with the proband's serum after a 6 h-incubation with lymphocytes of the same donor. Nineteen newly diagnosed diabetic patients, 23 persons at risk and 11 control probands were studied. There was no appreciable cytotoxic activity in the control probands (with one exception) and in 7 out of the 19 newly diagnosed diabetics. Five of the diabetes-susceptible probands developed diabetes mellitus during the investigation period. Anti-islet cytotoxicity of lymphocytes was found in these individuals at least 8 months before diagnosis of Type 1 diabetes. The cytotoxic effect disappeared at various time intervals after disease manifestation. Islet cytotoxicity was intermittently found with lymphocytes from further 13 probands at risk, sometimes for more than one year. Our data indicate that mononuclear cells from probands who are at high risk for developing Type 1 diabetes can exert cytotoxicity on xenogenic neonatal islets in the presence of their own serum.