Total Lymphoid Irradiation Prevents Diabetes Mellitus in the Bio-Breeding/Worcester (BB/W) Rat

Abstract

Total lymphoid irradiation (TLI) at doses of 2200 rads or greater prevented diabetes in susceptible BB/W rats. Two of 29 (7%) treated rats became diabetic compared with 23 of 39 (59%) controls (P less than 0.001). TLI did not, however, prevent insulitis or thyroiditis in nondiabetic rats, nor did it restore the depressed concanavalin-A responsiveness of BB rat lymphocytes. T-lymphocyte subset proportions were the same in both groups. TLI was associated with significant radiation-related mortality, and nondiabetic TLI-treated rats weighed significantly less than controls. We conclude that TLI is effective in the prevention of BB rat diabetes. However, TLI fails to correct the subclinical immunologic abnormalities of the model and is associated with significant morbidity.

Diabetes in the Bio-Breeding/Worcester rat. Induction and acceleration by spleen cell-conditioned media.

“…These values are similar to those of untreated W-line rats (n = 6) which averaged 13,000/mm3, 88% mononuclear cells, 10% polymorphonuclear cells, and 1% eosinophils. Splenic lymphocyte subset analysis of one diabetic W-line rat showed 20% OX8+ suppressor/cytotoxic cells and 26% W3/25+ helper cells, percentages comparable to those previously reported for nondiabetic W-line rats (9).…”

In vivo prevention of thyroid and pancreatic autoimmunity in the BB rat by antibody to class II major histocompatibility complex gene products.

“…Anti-lymphocyte serum (26), neonatal thymectomy (27), total lymphoid irradiation (28), cyclosporin A (29), and inoculation of bone marrow (30) have all been shown to prevent diabetes. These results support the concept that autoimmune reactions play a major role in the destruction of insulin-secreting cells responsible for the disease.…”

Prevention of diabetes in BB/Wor rats by intrathymic islet injection.

“…In addition, subjectively, the size of the pancreatic islets of protected animals appeared similar to the size ofthe islets in the pancreata ofcontrol, nondiabetic rats; thus a "shutting down" of the pancreatic islets did not seem to be occurring. (24) showed no changes in lymphocyte subsets after total lymphoid irradiation in diabetes-protected animals. Changes in the activity of lymphocytes within a given subset may have accounted for these, and our present, findings.…”