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 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.


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+ 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.


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.
Colson
Y L
YL
The Department of Surgery, University of Pittsburgh, Pennsylvania 15261, USA.
Abou El-Ezz
A Y
AY
Gaines
B A
BA
Ildstad
S T
ST
D000818:Animals; D000938:Antigen-Presenting Cells; D001853:Bone Marrow / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002455:Cell Division; D007519:Isoantigens / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011828:Radiation Chimera / Q000235:genetics / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013934:Thymectomy
D007519:Isoantigens; D016693:Receptors, Antigen, T-Cell, alpha-beta