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

J Immunol. 2007 Dec 1;179(11):7358-64. doi: 10.4049/jimmunol.179.11.7358.

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 down-regulation is regulated by lineage commitment signals.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • 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*
  • Receptors, CCR7 / immunology
  • Thymus Gland / cytology
  • Thymus Gland / growth & development*
  • Thymus Gland / immunology*
  • Transcription Factors / immunology
  • Up-Regulation / immunology

Substances

  • Ccr7 protein, mouse
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Ligands
  • Receptors, Antigen, T-Cell
  • Receptors, CCR7
  • Th-POK protein, mouse
  • Transcription Factors