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 language | English |
---|---|
Pages (from-to) | 7358-7364 |
Number of pages | 7 |
Journal | Journal of Immunology |
Volume | 179 |
Issue number | 11 |
DOIs | |
State | Published - 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