Self tolerance and localized autoimmunity. Mouse models of autoimmune disease that suggest tissue-specific suppressor T cells are involved in self tolerance.

Abstract

Autoimmune diseases appeared frequently in adults in the prostate and stomach of C3.129 mice after thymectomy on day 3 (Tx-3) without any additional treatment. Lesions of both organs could be completely prevented by a single i.p. injection of spleen cells from syngeneic adult mouse on day 4. For prevention of prostatitis, the most effective cell source was normal males (4 .times. 106); normal females or Orx-0 males were less effective as the cell source, and higher doses of cells (4 .times. 107) were needed. In contrast, spleen cells (4 .times. 106) from these three donors had equivalent capacity for the prevention of gastritis. Similar autoimmune prostatitis developed at very high frequency when spleen cells (4 .times. 106) from normal females or Orx-0 males, but not from normal males, were injected i.p. into C3.129 nu/nu mice at 4 d. However, no sign of prostatitis was found in nu/+ recipients. Injection of a larger dose (4 .times. 107) from the same donors was not effective for induction of prostatitis. Gastritis could not be induced in nu/nu mice by this procedure. Injection of spleen cells from Tx-3 males or females was effective for induction of both prostatitis and gastritis in nu/nu recipients. It was also shown that a T cell population (Thy-1.2+, Ig-) had the capacity to prevent and to induce autoimmune diseases. These results together strongly suggest a role for active tissue-specific suppressor T cells in self tolerance, and elimination of such T cell populations causes autoimmunity.