Positive and negative selection of alpha beta TCR+ T cells in thymectomized adult radiation bone marrow chimeras

Background. The mature T-cell repertoire is characterized by the negative s election of potentially autoreactive T cells and the positive selection of T cells restricted to antigen-recognition in the context of self-MHC molecu les, It is currently believed that the thymus is critical for these selecti on events. Although alpha beta T cell receptor (TCR)(+) T cells have been r eported in thymectomized recipients, whether this represents clonal expansi on 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 eva luated in adult radiation bone marrow chimeras prepared after complete surg ical thymectomy. Results. CD4(+) and CD8(+) T cells were present and exhibited donor-specifi c TCR-V beta expression and self-tolerance, indicative of negative selectio n. Positive selection was confirmed with the demonstration of host MHC rest riction and the presence of donor-derived CD8(+) T cells after the transpla ntation of marrow from Class I deficient donors into normal recipients. Conclusions. These data provide evidence, for the first time, that the deve lopment of a functional T-cell repertoire can occur in adult recipients wit hout the thymic microenvironment.