| First Author | Jiang D | Year | 1996 |
| Journal | J Exp Med | Volume | 183 |
| Issue | 4 | Pages | 1923-8 |
| PubMed ID | 8666950 | Mgi Jnum | J:110862 |
| Mgi Id | MGI:3641404 | Doi | 10.1084/jem.183.4.1923 |
| Citation | Jiang D, et al. (1996) p53 prevents maturation to the CD4+CD8+ stage of thymocyte differentiation in the absence of T cell receptor rearrangement. J Exp Med 183(4):1923-8 |
| abstractText | Rearrangement of the immunoglobulin (Ig) and T cell receptor (TCR) gene loci allows for the generation of B and T lymphocytes with antigen-specific receptors. Complete rearrangement and expression of the TCR-beta chain enables immature thymocytes to differentiate from the CD4-CD8- to the CD4+CD8+ stage mice in which rearrangement is impaired, such as severe combined immunodeficient (SCID) mice or recombinase activating gene-deficient (RAG-/-) mice, lack mature B and T lymphocytes. Thymocytes from these mice are arrested at the CD4-CD8- stage of T cell development. We previously observed that thymocytes from RAG-2-/- mice exposed to gamma radiation differentiate from CD4-CD8- into CD4+CD8+ without TCR-beta chain rearrangement. We now report that irradiated RAG-2-/- thymocytes undergo direct somatic mutations at the p53 gene locus, and that p53 inactivation is associated with maturation of RAG2-/- thymocytes to the CD4+CD8+ stage. Generation of RAG2-/- and p53-/- double-deficient mice revealed that, in the absence of TCR-beta chain rearrangement, loss of p53 function is sufficient for CD4-CD8- thymocytes to differentiate into the CD4+CD8+ stage of T cell development. Our data provide evidence for a novel p53 mediated checkpoint in early thymocyte development that regulates the transition of CD4-CD8- into CD4+CD8+ thymocytes. |
