Jb. Classen et Em. Shevach, POST-THYMECTOMY ORGAN-SPECIFIC AUTOIMMUNITY - ENHANCEMENT BY CYCLOSPORINE-A AND INHIBITION BY IL-2, Autoimmunity, 15(1), 1993, pp. 55-59
It has previously been shown that the administration of cyclosporine A
to newborn mice results in the development of autoimmunity later in l
ife. It has been proposed that the neonatal administration of cyclospo
rine A results in altered thymic selection or inhibition of the develo
pment of suppressor cells. In the present study, treatment of day 3 th
ymectomized C3H/HeN mice with cyclosporine A (20 mg/kg/day) for 9 d po
st surgery increased the prevalence of antigastric autoantibodies. In
contrast, the administration of IL-2 (300-600 Units/g/day) for 7 days
after thymectomy inhibited the development of antigastric antibodies.
We hypothesize that CsA may act by causing transient lymphokine abnorm
alities in the extrathymic environment during the first few weeks of l
ife which lead to the development of antigastric antibodies. In contra
st to the inhibition of development of antigastric antibodies, the adm
inistration of a similar course of IL-2 produced only a transient supp
ression of diabetes in NOD mice. These results and other data suggest
that diabetes in NOD mice is probably due to a different immunologic d
efect.