Precursor Thymocyte Proliferation and Differentiation Are Controlled by Signals Unrelated to the Pre-TCR

• Published in: The Journal of immunology (1950) 2000-09, Vol.165 (6), p.3094-3098
• Main Authors: Petrie, Howard T, Tourigny, Michelle, Burtrum, Douglas B, Livak, Ferenc
• Format: Article
• Language: English
• Subjects: Animals; Cell Death - genetics; Cell Death - immunology; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Division - genetics; Cell Division - immunology; Cell Survival - genetics; Cell Survival - immunology; Gene Expression Regulation - immunology; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; Genes, T-Cell Receptor beta; Lymphocyte Activation - genetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitosis - genetics; Mitosis - immunology; Receptors, Antigen, T-Cell, alpha-beta - biosynthesis; Receptors, Antigen, T-Cell, alpha-beta - deficiency; Receptors, Antigen, T-Cell, alpha-beta - genetics; Receptors, Antigen, T-Cell, alpha-beta - physiology; Signal Transduction - genetics; Signal Transduction - immunology; Stem Cells - immunology; Stem Cells - metabolism; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Thymus Gland - cytology; Thymus Gland - immunology; Thymus Gland - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.165.6.3094

In-frame rearrangement of the TCR-beta locus and expression of the pre-TCR are compulsory for the production of CD4+8+ thymocytes from CD4-8- precursors. Signals delivered via the pre-TCR are thought to induce the differentiation process as well as the extensive proliferation that accompanies this transition. However, it is equally possible that pre-TCR expression is required for the success of this transition, but does not play a direct role in the inductive process. In the present manuscript we examine this possibility using a variety of normal and genetically modified mouse models. Our evidence shows that differentiation and mitogenesis can both occur independently of pre-TCR expression. However, these processes are absolutely dependent on the presence of normal thymic architecture and cellular composition. These findings are consistent with a checkpoint role for the pre-TCR in regulating the divergence of survival and cell death fates at the CD4-8- to CD4+8+ transition. Further, our data suggest that precursor thymocyte differentiation is induced by other, probably ubiquitous, mechanisms that require the presence of normal thymic cellularity, composition, and architecture.