Prevention of diabetes and insulitis by neonatal intrathymic islet administration in NOD mice.
The murine model of human insulin dependent diabetes mellitus (IDDM), the non-obese diabetic (NOD) mouse, develops a T cell-dependent destruction of pancreatic islets. While the target antigens are unknown, there is clearly a lack of tolerance to them. Neonatal intrathymic (i.t.) antigen injection has been successfully employed to prevent insulitis in BB rats but previous i.t. islet antigen studies in NOD mice were done on older mice. We have injected syngeneic islets into the thymus of NOD mice at birth and found that diabetes and insulitis can be completely prevented by this procedure. The effect is islet antigen-specific since other T cell responses, including autoimmune salivary infiltration, ard unaffected. Furthermore, contrary to previous studies, cyclophosphamide administration was unable to induce diabetes in treated mice which suggests that deletion or anergy might be the mechanism by which neonatal intrathymic islet injection protects from disease. However, anti-islet antigen antibodies were still present in these mice which suggests that the mechanism of disease protection may be more complex.
Department of Medicine, Stanford University Medical School CA 94305.
B
B
Charlton
C
C
Taylor-Edwards
R
R
Tisch
C G
CG
Fathman
D000818:Animals; D000831:Animals, Newborn; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control* / Q000628:therapy; D007108:Immune Tolerance; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D007519:Isoantigens / Q000008:administration & dosage / Q000276:immunology*; D008198:Lymph Nodes / Q000473:pathology; D018655:Lymphocyte Count; D051379:Mice; D016688:Mice, Inbred NOD; D012793:Sialadenitis / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets; D013950:Thymus Gland / Q000276:immunology*; D016042:Transplantation, Heterotopic
D007519:Isoantigens