Combined deletion of CD8 locus cis-regulatory elements affects initiation but not maintenance of CD8 expression.
Developmental stage-, subset-, and lineage-specific CD8 enhancers have been identified recently by transgenic reporter analyses. Enhancer E8(II) (CIV-4,5) is active in both immature double-positive thymocytes (DP) and mature CD8 single-positive (SP) thymocytes and T cells, whereas E8(I) (CIII-1,2) directs expression only in mature cells. In mice lacking either E8(I) (CIII-1,2) or E8(II) (CIV-4,5), there was no effect on CD8 expression in DP thymocytes. However, deletion of both enhancers resulted in variegated expression of CD8, with appearance of CD4(+)CD8(-) SP thymocytes expressing surface markers characteristic of DP thymocytes. Consequently, fewer mature CD8(+) T cells developed from the reduced pool of DP cells. These results suggest that the initiation of CD8 expression is mediated by cis-regulatory elements that are distinct from any that may be involved in maintenance of expression.
Ellmeier
Wilfried
W
Institute of Immunology, University of Vienna, Vienna, Austria. wilfried.ellmeier@univie.ac.at
Sunshine
Mary Jean
MJ
Maschek
Romana
R
Littman
Dan R
DR
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D004742:Enhancer Elements, Genetic; D004848:Epithelium / Q000276:immunology; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D051379:Mice; D009924:Organ Culture Techniques; D012045:Regulatory Sequences, Nucleic Acid; D017384:Sequence Deletion; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology*; D015533:Transcriptional Activation
D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain