Cell components required for deletion of an autoreactive T cell repertoire

Publisher Website
Google Scholar
Abstract
T cells become tolerant to self antigens during their development in the thymus. Clonal deletion of thymocytes bearing T cell receptor (TcR) which recognize self antigens is a major mechanism for generating tolerance. In the present study we have used allogeneic bone marrow (BM) chimeras, prepared with various combinations of mouse strains and focusing especially on expressions of I‐E molecules and Mls‐1a antigens on the cell surface, to investigate both immuno‐histochemically and by flow cytometry the cell components that contribute to the clonal deletion of T cells positive for Vβ6 TcR. The Vβ6 TcR expression is strongly associated with T cell recognition of both I‐E and Mls‐1a antigens. We found that I‐E+ cells derived from donor BM (and thus not of recipient lineage) represented a primary requirement for deletion of Mls‐1a−reactive thymocytes which bear Vβ6 TcR. Immunohistochemical analysis revealed that the donor‐derived I‐E+ cells were distributed mainly to the thymic medulla and that the Vβ6+ cells were eliminated from the thymic medulla between 2 and 3 weeks following BM transplantation. In contrast, Mls‐1a+ cells of either donor or recipient origin might be responsible for the deletion, even though cortical epithelial cells appeared not to express Mls‐1a antigens.