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Precursor thymocyte proliferation and differentiation are controlled by signals unrelated to the pre-TCR

Academic Article
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Overview

authors

  • Petrie, Howard
  • Tourigny, M.
  • Burtrum, D. B.
  • Livak, F.

publication date

  • 2000

journal

  • Journal of Immunology  Journal

abstract

  • 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.

subject areas

  • Animals
  • Cell Death
  • Cell Differentiation
  • Cell Division
  • Cell Survival
  • Gene Expression Regulation
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • Genes, T-Cell Receptor beta
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitosis
  • Receptors, Antigen, T-Cell, alpha-beta
  • Signal Transduction
  • Stem Cells
  • T-Lymphocyte Subsets
  • Thymus Gland
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Identity

International Standard Serial Number (ISSN)

  • 0022-1767

PubMed ID

  • 10975821
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Additional Document Info

start page

  • 3094

end page

  • 3098

volume

  • 165

issue

  • 6

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