Positive and negative selection of alphabetaTCR+ T cells in thymectomized adult radiation bone marrow chimeras.

Background. The mature T-cell repertoire is characterized by the negative selection of potentially autoreactive T cells and the positive selection of T cells restricted to antigen-recognition in the context of selfMHC molecules. It is currently believed that the thymus is critical for these selection events. Although abT cell receptor (TCR) 1 T cells have been reported in thymectomized recipients, whether this represents clonal expansion of residual T cells or de novo generation of new T cells in the absence of a thymus has not been definitively evaluated. Methods. In the current study, development of the T-cell repertoire was evaluated in adult radiation bone marrow chimeras prepared after complete surgical thymectomy. Results. CD4 1 and CD8 1 T cells were present and exhibited donor-specific TCR-Vb expression and selftolerance, indicative of negative selection. Positive selection was confirmed with the demonstration of host MHC restriction and the presence of donor-derived CD8 1 T cells after the transplantation of marrow from Class I deficient donors into normal recipients. Conclusions. These data provide evidence, for the first time, that the development of a functional T-cell repertoire can occur in adult recipients without the thymic microenvironment. Positive and negative selection are two essential events in T-cell development that result in the generation of a mature abT cell receptor (TCR) 1 T-cell repertoire. Both are active processes believed to critically depend on specific events, which occur within the thymus (1‐5). Burnett postulated more than 35 years ago that clonal deletion of potentially autoreactive T cells is the mechanism primarily responsible for the acquisition of immunologic self-tolerance (6). Clonal deletion has been demonstrated to be a result of the intrathymic deletion of immature thymocytes, which respond too strongly to bone marrow-derived dendritic cells within the thymus. Positive selection results in the recruitment of thymocytes capable of interacting with antigens only when complexed with the self-MHC molecules expressed on thymic epithelial cells. Without the thymic microenvironment, T-cell