Cellular immunity to human insulin in individuals at high risk for the development of type I diabetes mellitus.
In order to investigate the role of insulin as a potential target autoantigen of cellular immunity in the prediabetic period, proliferative responses of T lymphocytes to human insulin were studied in nine islet-cell antibody (ICA) + first-degree relatives of patients with Type I diabetes (individuals at high risk for the development of Type I diabetes, or the 'prediabetic' group, which was never treated with insulin) and in 12 control individuals. Insulin autoantibodies were present in 6/9 (67%) of the prediabetic subjects and none of the controls. Peripheral blood lymphocytes were collected on Ficoll and incubated with human insulin, control antigens, or media alone for 5-6-day and 9-10-day incubation periods. Cells were pulsed with 3H-thymidine, harvested, and analysed in a scintillation counter. Results are expressed as stimulation index (SI = cpm with antigen/cpm without antigen), with a SI greater than or equal to 1.5 considered a positive response. Eight of nine (89%) prediabetic individuals responded positively to insulin after a 9-10-day incubation period, in contrast to four of 12 (33%) control subjects, P less than 0.05. The mean proliferative response to insulin after 9-10 days' incubation was 2.1 +/- 0.4 and 1.2 +/- 0.1, for the prediabetic and control groups, respectively. The proliferative response to insulin was not directly correlated with levels of insulin autoantibodies (r = -0.05, NS). These data suggest that most individuals at high risk for the development of Type I diabetes display a cellular immune response to insulin, and a subset of these individuals does not display a concomitant humoral immune response to insulin based on the presence or absence of insulin autoantibodies.
Keller
R J
RJ
Children's Hospital, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02115.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D006801:Humans; D007328:Insulin / Q000276:immunology* / Q000502:physiology; D007330:Insulin Antibodies / Q000097:blood; D007515:Islets of Langerhans / Q000276:immunology; D008213:Lymphocyte Activation; D008875:Middle Aged; D011236:Prediabetic State / Q000276:immunology*; D051381:Rats; D011919:Rats, Inbred Strains; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; D007328:Insulin; D007330:Insulin Antibodies