Induction of T cell CD7 gene transcription by nonmitogenic ionomycin-induced transmembrane calcium flux.
The CD7 molecule is a 40-kDa member of the Ig superfamily that has structural homology to the murine Thy-1 molecule and is acquired early in human T cell ontogeny. Previous studies have demonstrated that expression of the CD7 molecule is markedly up-regulated during T cell activation. In this study, we have studied the signals required for CD7 up-regulation on human T cells. We found that nonmitogenic amounts of ionomycin selectively and maximally up-regulated T cell CD7 on mature (peripheral blood) T cells after 24 h. Whereas CD7 expression was increased 78 +/- 25% by 0.5 microM ionomycin, expression of CD25 (IL-2R alpha), class II MHC, 4F2, transferrin receptor, CD2, CD3, CD4, CD5, and CD8 molecules was not increased. Ionomycin-induced CD7 surface expression was associated with peak increases in CD7 mRNA after 4 to 6 h. Transcriptional analysis and CD7 mRNA half-life determination revealed the increase in CD7 mRNA was the result of increased CD7 gene transcription 1 h after ionomycin stimulation and was not due to prolongation of CD7 mRNA half-life. The up-regulation of surface CD7 expression by ionomycin was dependent on extracellular calcium and did not require the activation of T cell tyrosine protein kinase. Mitogenic CD2 and CD3 mAb as well as stimulation of T cells by PHA also up-regulated CD7 expression. CD7 up-regulation by ionomycin was transient (24 to 72 h) and inhibitable by cyclosporin A, whereas CD7 up-regulation by PHA was sustained over 5 to 7 days and was significantly less inhibitable by cyclosporin A. These data demonstrate that induction of a transmembrane calcium flux generates signals that lead to CD7 gene transcription.
Ware
R E
RE
Department of Medicine, Duke University Medical Center, Durham, NC 27710.
Hart
M K
MK
Haynes
B F
BF
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics*; D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D018801:CD2 Antigens; D017252:CD3 Complex; D002118:Calcium / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D006207:Half-Life; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology*; D010835:Phytohemagglutinins; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D016207:Cytokines; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D015759:Ionomycin; D016572:Cyclosporine; D011505:Protein-Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium