Dysregulated expression of pre-Tα reveals the opposite effects of pre-TCR at successive stages of T cell development

H. D. Lacorazza, H. E. Porritt, J. Nikolich-Žugich

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The pre-TCR complex (TCRβ-pre-TCRα chain (pTα)), first expressed in a fraction of CD8-4-CD44-25+ (DN3) cells, is believed to facilitate or enable an efficient transition from the CD8-4- double-negative (DN) to the CD8+4+ double-positive (DP) developmental stage. Subsequent to pre-TCR expression, DN3 thymocytes receive survival, proliferation, and differentiation signals, although it is still unclear which of these outcomes are directly induced by the pre-TCR. To address this issue, we generated mice bearing a range of ptα transgene copy number under the transcriptional control of the p56lck proximal promoter. All lines exhibited increased DN3 cycling, accelerated DN3/4 transition, and improved DN4 survival. However, the high copy number lines also showed a selective reduction in thymic cellularity due to increased apoptosis of DP thymocytes, which could be reversed by the ectopic expression of Bcl-2. Our results suggest that transgenic ptα likely caused apoptosis of DP thymocytes due to competitive decrease in surface TCRαβ formation. These results highlight the critical importance of precise temporal and stoichiometric regulation of pre-TCR and TCR component expression.

Original languageEnglish (US)
Pages (from-to)5689-5696
Number of pages8
JournalJournal of Immunology
Volume167
Issue number10
DOIs
StatePublished - Nov 15 2001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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