T cell tolerance to non-H-2-encoded stimulatory alloantigens is induced intrathymically but not prethymically.

Abstract

The differentiation compartment in which T cells are tolerized to non-major histocompatibility complex (MHC)-encoded minor lymphocyte-stimulating locus (MLS) alloantigens was evaluated. T cell precursors were not tolerized prethymically to MLS alloantigens but were tolerized intrathymically and postthymically to MLS alloantigens. The failure of prethymic T cells to be tolerized indicates that T cell precursors are unable to be tolerized to MLS alloantigens or that cells in the prethymic compartment are unable to induce MLS-specific tolerance. The thymus is evidently the initial site in which T cell tolerance to MLS alloantigen is induced. A striking disparity in the reactivity of thymocyes to MHC and MLS alloantigens expressed in the extrathymic host through which their precursors had migrated was demonstrated. In the experimental mice constructed for these studies, intrathymic T cells were tolerant to the MHC alloantigens but were reactive to the MLS alloantigens expressed by the extrathymic host. Evidently, T cell precursors are tolerized to MHC alloantigens at an earlier point in their differentiation than they are tolerized to non-MHC-encoded MLS alloantigens.