Autoimmune thyroiditis induced in mice depleted of particular T cell subsets. III. Analysis of regulatory cells suppressing the induction of thyroiditis.

It has previously been demonstrated that T cell clones with potentials to induce autoimmune thyroiditis exist in lymphoid organs from normal healthy individuals. The present study investigates the nature of regulatory cells co-existing in a normal lymphoid cell population to prevent the activation of these thyroiditis-inducing T cells. T cell-depleted (C57BL/6 x C3H/He) F1 mice (B cell mice) were prepared by adult thymectomy and injection of anti-thymocyte serum, followed by lethal X-irradiation and bone marrow reconstitution. Typical thyroiditis was induced in these B cell mice by i.v. administration of Lyt-1dull T cells but not of whole T cells from normal syngeneic mice. Additional injection of normal thymocytes into B cell mice which had been transferred with the Lyt-1 dull T cells resulted in complete prevention of thyroiditis induction. Mature thymocytes were responsible for this regulatory function and such regulatory cell activity was also found in peripheral lymphoid cells such as spleen cells. These regulatory cells exerted their capacity to prevent thyroiditis in cell dose-dependent and injection timing-dependent manners; thyroiditis was prevented when they were injected in cell doses of greater than 1.5 x 10(7)/mouse and before the initiation of the thyroiditis lesion. Most interestingly, the phenotypes of regulatory cells were Thy-1+ and L3T4+. Since the thyroiditis-inducing Lyt-1 dull T cells has previously been shown to be of L3T4+, these results indicate that there exist functionally heterogeneous subsets in an L3T4+ T cell population and that some L3T4+ T cells function as regulatory cells to prevent the activation of thyroiditis-inducing L3T4+ T cells co-existing in the normal lymphoid cell population.