Induction of Central Tolerance by Mature T Cells

Induction of immunological tolerance is highly desirable for the treatment and prevention of autoimmunity, allergy, and organ transplant rejection. Adoptive transfer of MHC class I disparate mature T cells at the time of reconstitution of mice with syngeneic bone marrow resulted in specific tolerance to allogeneic skin grafts that were matched to the T cell donor strain. Mature allogeneic T cells survived long-term in reconstituted hosts and were able to re-enter the thymus. Analysis of T cell development using transgenic mice expressing an alloantigen-reactive TCR revealed that expression of allogeneic MHC class I on adoptively transferred mature T cells mediated negative selection of developing alloreactive T cells in the thymus. Thus, mature allogeneic T cells are able to mediate central deletion of alloreactive cells and induce transplantation tolerance without the requirement for any other alloantigen-expressing cell type.