THE DIFFERENTIATION OF HUMAN PRO-THYMOCYTES ALONG THE TCR-ALPHA/BETA PATHWAY INVITRO IS ACCOMPANIED BY THE SITE-SPECIFIC DELETION OF THE TCR-DELTA LOCUS

The nested location of the TCR-delta gene within the TCR-alpha locus is a common feature of both mouse and human. Yet alpha/beta and gamma/delta T cells represent two separate lineages. We have previously proposed that a specific rearrangement event (delta-Rec-PSI-J-alpha) resulting in the specific deletion of the TCR-delta gene could be responsible for the independent usage of these two loci. We used an in vitro model of T cell differentiation to test this hypothesis. We show that in culture conditions (IL-1 + sCD23) which promote the development of alpha/beta expressing T cells exclusively, the specific deletion of the TCR-delta locus occurs very rapidly, probably before the productive rearrangement of the TCR-alpha gene. These results clearly demonstrate that the specific deletion of the TCR-delta gene could be the initial regulatory event that imprints the irreversible commitment of T cell differentiation along the alpha/beta pathway.