CCR7 expression in developing thymocytes is linked to the CD4 versus CD8 lineage decision

Xinye Yin, Ena Ladi, Wei Chan Shiao, Li Ou, Nigel Killeen, Dietmar J. Kappes, Ellen A. Robey

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

During thymic development, T cell progenitors undergo positive selection based on the ability of their T cell Ag receptors (TCR) to bind MHC ligands on thymic epithelial cells. Positive selection determines T cell fate, in that thymocytes whose TCR bind MHC class I (MHC-I) develop as CD8-lineage T cells, whereas those that bind MHC class II (MHC-II) develop as CD4 T cells. Positive selection also induces migration from the cortex to the medulla driven by the chemokine receptor CCR7. In this study, we show that CCR7 is up-regulated in a larger proportion of CD4+CD8+ thymocytes undergoing positive selection on MHC-I compared with MHC-II. Mice bearing a mutation of Th-POK, a key CD4/CD8-lineage regulator, display increased expression of CCR7 among MHC-II-specific CD4+CD8+ thymocytes. In addition, overexpression of CCR7 results in increased development of CD8 T cells bearing MHC-II-specific TCR. These findings suggest that the timing of CCR7 expression relative to coreceptor downregulation is regulated by lineage commitment signals.

Original languageEnglish
Pages (from-to)7358-7364
Number of pages7
JournalJournal of Immunology
Volume179
Issue number11
DOIs
StatePublished - Dec 1 2007

Keywords

  • Animals
  • CD4-Positive T-Lymphocytes/cytology
  • CD8-Positive T-Lymphocytes/cytology
  • Cell Differentiation/immunology
  • Cell Lineage/immunology
  • Histocompatibility Antigens Class I/immunology
  • Histocompatibility Antigens Class II/immunology
  • Ligands
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Protein Binding
  • Receptors, Antigen, T-Cell/immunology
  • Receptors, CCR7/biosynthesis
  • Thymus Gland/cytology
  • Transcription Factors/immunology
  • Up-Regulation/immunology

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