The differentiation of human pro-thymocytes along the TCR-alpha/beta pathway in vitro 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.
de Villartay
J P
JP
Laboratoire d'Immunologie et Rhumatologie pédiatrique (INSERM U132), Hôpital Necker-Enfants-Malades, Paris, France.
Mossalayi
D
D
de Chasseval
R
R
Dalloul
A
A
Debré
P
P
D001483:Base Sequence; D002454:Cell Differentiation; D002872:Chromosome Deletion; D015329:Gene Rearrangement, T-Lymphocyte; D005796:Genes; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology
D009841:Oligonucleotides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta