Administration of anti-interleukin-2 receptor alpha antibody in vivo induces localized autoimmune disease

Neonatal thymectomy (Tx) of mice at day 3 after birth (Tx-3), but not day 7 (Tx-7), induces organ-localized autoimmune diseases such as oophoritis and gastritis. Lesions in Tx-3 mice can be prevented by injection of splenic CD4(+) cells from syngeneic normal mice, and this CD4(+) population with suppressor activity is activated extrathymically by self antigens. Since it is speculated that these CD4(+) T suppressor cells (Ts) express the interleukin-2 receptor (IL-2R) as an activated T cell population, an attempt was made to eliminate these Ts from the developing immune system of Tx-7 mice and normal mice by i.p. injection of anti-IL-2R alpha monoclonal antibodies. Interestingly, organ-localized autoimmune disease with quite similar characteristics to those observed after neonatal Tx developed in not only Tx-7 mice, but also normal mice. The results thus indicate that CD4(+) cells expressing IL-2R alpha play an important role, as Ts in the periphery, in maintaining immune tolerance.