T-LYMPHOCYTES FROM HUMAN CHIMERAS DO RECOGNIZE ANTIGEN IN THE CONTEXT OF ALLOGENEIC DETERMINANTS OF THE MAJOR HISTOCOMPATIBILITY COMPLEX

Human stem cells from the fetal liver can be transplanted to immunodeficient patients and reconstitute their immunity by giving rise to immunocompetent T lymphocytes of donor origin. Despite full HLA mismatch between donor and host, the helper T cells and the cytotoxic T cells which develop in these chimeric patients are totally functional. They recognize the antigenic peptides presented in the context of the foreign HLA molecules of the recipient, indicating that donor stem cells have been positively selected in the host environment, probably the thymic epithelial cells. By contrast, negative selection appears to be imposed upon T cells by donor hemopoietic cells, probably macrophages or dendritic cells, migrating from the transplant to the host thymus. Clonal deletion is then responsible for tolerance to donor HLA antigens, while clonal anergy explains tolerance to host HLA antigens.