CCR7 expression in developing thymocytes is linked to the CD4 versus CD8 lineage decision.
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.
Yin
Xinye
X
Department of Molecular and Cell Biology, Division of Immunology, University of California, Berkeley, CA 94720, USA.
Ladi
Ena
E
Chan
Shiao Wei
SW
Li
Ou
O
Killeen
Nigel
N
Kappes
Dietmar J
DJ
Robey
Ellen A
EA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D054400:Receptors, CCR7 / Q000096:biosynthesis* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development* / Q000276:immunology*; D014157:Transcription Factors / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D054400:Receptors, CCR7; D014157:Transcription Factors; C515371:Ccr7 protein, mouse; C497211:Zbtb7b protein, mouse