Acceleration of the onset of diabetes in NOD mice by thymectomy at weaning.
The effect of thymectomy performed at weaning (3 weeks) and at 6-7 weeks of age on the incidence of diabetes was examined in the non-Obese diabetic (NOD) mouse, a spontaneous model of immunologically mediated insulin-dependent diabetes similar to human type I diabetes. When performed at weaning, thymectomy led to a dramatic increase in the incidence of diabetes in NOD females in comparison to sham-thymectomized animals. Conversely, no change in the incidence of the disease or the expression of insulitis was noted when thymectomy was performed in NOD males. When delayed beyond 6-7 weeks of age, thymectomy had no effect on NOD males and females. Flow cytometry analysis of spleen cells from intact mice and mice thymectomized at weaning or at 6-7 weeks of age demonstrated a significant depletion of the T cell subsets in both groups of thymectomized animals. These results indicate that the onset of diabetes in NOD mice is submitted to thymic regulation and that the T cell depletion induced by thymectomy at weaning accelerates the disease, an effect possibly due to the loss of some T cell-dependent suppressor mechanisms.
Dardenne
M
M
INSERM U 25 and CNRS UA 122, Hôpital Necker, Paris, France.
Lepault
F
F
Bendelac
A
A
Bach
J F
JF
D000367:Age Factors; D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology*; D005260:Female; D007515:Islets of Langerhans / Q000473:pathology; D008297:Male; D051379:Mice; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000145:classification / Q000502:physiology*; D013934:Thymectomy; D014886:Weaning