The differentiation of human pro-thymocytes along the TCR-α/β pathway in vitro is accompanied by the site-specific deletion of the TCR-δ locus

• Published in: International immunology 1991-12, Vol.3 (12), p.1301-1305
• Main Authors: de Villartay, Jean-Pierre, Mossalayi, Djavad, de Chasseval, Regina, Dalloul, Alli, Debré, Patrice
• Format: Article
• Language: English
• Subjects: Base Sequence; CD23; Cell Differentiation; Chromosome Deletion; differentiation; Gene Rearrangement, T-Lymphocyte; gene regulation; Genes; Humans; In Vitro Techniques; Molecular Sequence Data; Oligonucleotides - chemistry; Polymerase Chain Reaction; Receptors, Antigen, T-Cell, alpha-beta - genetics; Receptors, Antigen, T-Cell, gamma-delta - genetics; T cell receptor; T-Lymphocytes - cytology; thymus; Thymus Gland - cytology
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/3.12.1301

The nested location of the TCR-δ gene within the TCR-α locus is a common feature of both mouse and human. Yet α/β and γ/δ T cells represent two separate lineages. We have previously proposed that a specific rearrangement event (δRec-ψJα) resulting in the specific deletion of the TCR-δ 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 α/β expressing T cells exclusively, the specific deletion of the TCR-δ locus occurs very rapidly, probably before the productive rearrangement of the TCR-α gene. These results clearly demonstrate that the specific deletion of the TCR-δ gene could be the initial regulatory event that imprints the irreversible commitment of T cell differentiation along the α/β pathway.