T cell CD7 mRNA expression is regulated by both transcriptional and post-transcriptional mechanisms.
The CD7 molecule is a 40 kDa member of the Ig superfamily that is acquired early in human T cell ontogeny. Because of the putative three-dimensional structure of CD7 and its presence on T cell precursors, it has been postulated that CD7 serves as an adhesion molecule that facilitates early T cell maturation. Ligand binding to CD7 on mature peripheral blood (PB) T cells has been reported to deliver a co-mitogenic signal with CD3 mAb for T cell triggering. In previous work, we found that CD7 was upregulated on PB T cells following a non-mitogenic ionomycin-induced transmembrane calcium flux, which induced new T cell CD7 transcription without affecting CD7 mRNA stability. In this report, we have studied the upregulation of CD7 expression on PB T cells following stimulation by ionomycin, phytohemagglutinin (PHA), and CD3 mAb. PHA prolonged T cell CD7 mRNA stability without affecting CD7 transcription, while stimulation of PB T cells with CD3 mAb both increased T cell CD7 transcription and prolonged CD7 mRNA stability. Experiments with cycloheximide demonstrated superinduction of T cell CD7 mRNA and showed that new protein synthesis was not required for ionomycin-induced upregulation of T cell CD7 expression. Cyclosporin A inhibited ionomycin-induced T cell CD7 upregulation at the level of CD7 mRNA transcription and elongation. These data demonstrate that ionomycin, PHA, and CD3 mAb act via different mechanisms to increase T cell CD7 expression, and that both transcriptional and post-transcriptional mechanisms are used to modify CD7 mRNA levels.
Ware
R E
RE
Department of Pediatrics, Duke University Medical Center, Durham, NC 27710.
Haynes
B F
BF
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis* / Q000235:genetics; D001483:Base Sequence; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D008969:Molecular Sequence Data; D010835:Phytohemagglutinins / Q000494:pharmacology; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D015759:Ionomycin; D016572:Cyclosporine; D003513:Cycloheximide