Precursor Thymocyte Proliferation and Differentiation Are Controlled by Signals Unrelated to the Pre-TCR
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 t...
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Published in | The Journal of immunology (1950) Vol. 165; no. 6; pp. 3094 - 3098 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
Am Assoc Immnol
15.09.2000
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0022-1767 1550-6606 |
DOI: | 10.4049/jimmunol.165.6.3094 |