Natural Killer Cell and Islet Killer Cell Activities in Human Type 1 Diabetes

Summary

Peripheral blood mononuclear cells from 14 type 1 diabetic patients were examined for natural killer cell activity using the K562 cell line as 51Cr labeled targets. Mean cytotoxicity of K562 cells by unseparated mononuclear cells derived from new onset type 1 patients (12 ± 1.6%) was lower (P > .01) than that observed in non diabetic controls, (25 ± 4.2%). Mean natural killer cell cytotoxicity mediated by enriched non-T cells from patients (41 ± 5.8%) was also lower (P > 0.03) than in the control group (56 ± 3.7 %). Specificity of these findings was evaluated by also examining other diabetic patient subgroups. Mean non T cell mediated natural killer cell activity in type 2 diabetic patients and type 1 patients with long term disease was 65 ± 5.4% and 62 ± 4.8% respectively (p > 0.001 vs new onset type 1 patients). Longitudinal studies of new onset type 1 patients during the remission (honeymoon) phase revealed no improvement of impaired natural killer cell activity.

In 30 new onset and 11 remission diabetic patiente, mean non-T cell-mediated cytotoxicity was also measured using dispersed ⁵¹Cr labeled pancreatic islet target cells. Mean islet cytotoxicity mediated by cells from new onset patients was 34 ± 2.4%, whereas in, nondiabetic control subjects mean cytotoxicity was 25 ± 1.8% (p > 0.005). During remission, islet cytotoxicity returned to normal values in over half of the patients. There was no correlation between K562 and islet cell cytotoxicity in either of the latter two patient groups. These results suggest a dichotomy in natural killer cell and islet killer cell activities in type 1 diabetes. These abnormalities could have important roles in the pathogenesis of type 1 diabetes.

Key words

Natural killer cells - Islet cytotoxicity