An enhancer that directs lineage-specific expression of CD8 in positively selected thymocytes and mature T cells.
Positive selection of CD4+CD8+ T cells to the CD4+CD8- helper and CD4- CD8+ cytotoxic lineages is a multistep process that involves complex regulation of coreceptor gene expression. By analyzing expression of a reporter gene in transgenic mice, we have identified a DNA segment, located between the murine CD8beta and CD8alpha genes, that has enhancer activity restricted to CD8 lineage cells. Remarkably, this enhancer functions in thymocytes undergoing positive selection to the CD4-CD8+ phenotype but not in immature double-positive thymocytes. The enhancer also functions in gut intraepithelial lymphocytes that express CD8alpha but not CD8beta, suggesting that it is specific for CD8alpha expression. The tight correlation between activation of this enhancer and the final step in positive selection has important implications for understanding the mechanism of lineage commitment in thymocytes.
Ellmeier
W
W
Division of Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, New York University Medical Center, New York 10016, USA.
Sunshine
M J
MJ
Losos
K
K
Hatam
F
F
Littman
D R
DR
D000818:Animals; D018801:CD2 Antigens / Q000235:genetics; D016827:CD8 Antigens / Q000235:genetics*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018983:DNA Footprinting; D003850:Deoxyribonuclease I; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D006801:Humans; D018928:Immunity, Mucosal; D019891:Leukopoiesis; D051379:Mice; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology; D014158:Transcription, Genetic
D018801:CD2 Antigens; D016827:CD8 Antigens; D003850:Deoxyribonuclease I