Insulin treatment prevents diabetes mellitus but not thyroiditis in RT6-depleted diabetes resistant BB/Wor rats.
Prophylactic insulin administration is known to prevent hyperglycaemia in diabetes prone BB rats and non-obese diabetic mice. This study investigated the effect of insulin treatment on the development of overt diabetes, clinically inapparent anti-islet autoreactivity, and thyroiditis in RT6-depleted diabetes resistant BB rats. Fewer than 1% of these animals develop spontaneous diabetes, but if depleted of RT6- T cells greater than 50% become hyperglycaemic. We treated 30-day-old diabetes resistant rats with anti-RT6.1 monoclonal antibody, exogenous insulin, or both. Up to 60 days of age, 16 of 20 rats given antibody alone became diabetic, compared with 1 of 20 also treated with antibody plus insulin. Up to 110 days of age, only 1 of 10 rats treated with both insulin and antibody between 30 and 60 days became diabetic. Histologic study of non-diabetic insulin plus anti-RT6 antibody treated rats revealed insulitis in 3 of 9 at 60 days old, and insulitis in 3 of 8 and thyroiditis in 6 of 7 at 110 days of age. Non-diabetic animals were also found to harbour autoreactive spleen cells that adoptively transferred diabetes. Splenocytes from 60 or 110-day-old non-diabetic donors that had been treated with insulin and antibody between 30 and 60 days of age induced diabetes in 7 of 13 and 6 of 8 adoptive recipients respectively. We conclude that insulin treatment prevents clinical diabetes in the RT6-depleted diabetes resistant BB rat, but this treatment does not prevent the development of autoreactive cell populations that cause thyroiditis and adoptively transfer diabetes.
Gottlieb
P A
PA
Department of Medicine, University of Massachusetts Medical School, Worcester.
Handler
E S
ES
Appel
M C
MC
Greiner
D L
DL
Mordes
J P
JP
Rossini
A A
AA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D007113:Immunity, Innate; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D007328:Insulin / Q000627:therapeutic use*; D007515:Islets of Langerhans / Q000276:immunology; D008212:Lymphocyte Depletion; D051381:Rats; D011913:Rats, Inbred BB; D013601:T-Lymphocytes / Q000276:immunology*; D013966:Thyroiditis / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007328:Insulin; C024211:islet cell antibody