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

Abstract

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 self-MHC molecules. It is currently believed that the thymus is critical for these selection events. Although alpha(beta)T cell receptor (TCR)+ 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. In the current study, development of the T cell repertoire was evaluated in adult radiation bone marrow chimeras prepared after complete surgical thymectomy. CD4+ and CD8+ T cells were present and exhibited donor-specific TCR-Vbeta expression and self-tolerance, indicative of negative selection. Positive selection was confirmed with the demonstration of host MHC restriction and the presence of donor-derived CD8+ T cells after the transplantation of marrow from Class I deficient donors into normal recipients. 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.