Insulin prevents adoptive cell transfer of diabetes in the autoimmune non-obese diabetic mouse.
Early intensive insulin treatment is thought to improve subsequent Beta-cell function in Type 1 (insulin-dependent) diabetic patients. Prophylactic insulin administration also reduced diabetes incidence in diabetes-prone animals. To study the mechanisms by which these effects occur, we tested the ability of insulin therapy in the model of non-obese-diabetic mice, to prevent the penetration of committed T cells into the islets and subsequent Beta-cell destruction. Sublethally irradiated non-obese-diabetic males of 8 weeks of age were adoptively transferred with splenocytes from diabetic donors and treated with the maximum tolerable dosage of fast-acting insulin (0.5 U, twice daily) until 30 days after cell transfer. Diabetes incidence was compared to control animals injected with the same concentration of insulin diluent. After one month of treatment, the cumulative diabetes frequency was significantly less within the insulin-treated group (4 of 15, 26.6%) than in the control group (15 of 18, 83.3%; p less than 0.01). Pancreatic histological analysis of insulin-treated animals revealed a lower severity of insulitis and Beta-cell necrosis and a higher percentage of normal islets (46.6 +/- 10% vs 2.3 +/- 2%, p less than 0.01), including five (33%) mice with no lesions. Immunoperoxydase staining of pancreatic sections indicated similar insulin and ganglioside staining of Beta cells from insulin-treated mice and control animals. Insulin-treated mice had comparable pancreatic insulin content to normal mice. Flow cytometry analysis of spleen cell populations indicated that insulin increased the number of Thy1,2+ and Lyt-2+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Thivolet
C H
CH
INSERM U197, Lyon, France.
Goillot
E
E
Bedossa
P
P
Durand
A
A
Bonnard
M
M
Orgiazzi
J
J
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D005260:Female; D016219:Immunotherapy, Adoptive; D007328:Insulin / Q000627:therapeutic use*; D007330:Insulin Antibodies / Q000032:analysis*; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
D007328:Insulin; D007330:Insulin Antibodies