Tissue-specific suppressor T cells involved in self-tolerance are activated extrathymically by self-antigens

Autoimmune prostatitis developed spontaneously in (C57BL/6N x A/J)F1 (B6A) mice, when thymectomy (Tx) was conducted on day 3 after birth (Tx-3). The lesion could be prevented by a single injection of CD4+ spleen cells (4 x 10(6)) from normal males, but not from normal females or newborn orchidectomized (Orx-0) mice. However, when spleen cells were obtained from Orx-0 mice that had received a dihydrotestosterone (DHT) pellet when adult to develop a mature prostate, prostatitis could be prevented, suggesting that immune tolerance to prostate antigen(s) is maintained by a CD4+ tissue-specific suppressor T cell (Ts) population(s), which is activated by a specific autoantigen(s) in the mature prostate. The result that even CD4+ cells from Orx-0 mice that were thymectomized as adults and treated thereafter with DHT were effective for prevention of prostatitis suggests that activation of this Ts population takes place in the peripheral lymphoid organs, and that it maintains peripheral tolerance to autoantigen in the prostate of these mice and probably also in normal mice.