Correlation between up-regulation of lymphokine mRNA and down-regulation of TcR, CD4, CD8 and lck mRNA as shown by the effect of CsA on activated T lymphocytes.
Full activation of different T cell populations via the TcR/CD3 complex leads to transient expression of lymphokine mRNA and to transient and specific down-modulation of TcR, CD4, CD8 and p56lck mRNA (Multi-Receptor Complex or MRC mRNA). This transient down-modulation is due to both a decrease in transcription and stability of these mRNA and is temporally and quantitatively related to lymphokine mRNA induction. We showed that cyclosporin A (CsA), which blocks lymphokine expression also inhibits MRC mRNA down-modulation at the transcriptional level, and does not affect mRNA stability. The fact that CsA inhibits both lymphokine expression and MRC mRNA down-modulation at transcriptional level supports a model in which similar signals trigger the inverse regulation of these two sets of genes via identical transcriptional factors.
Paillard
F
F
INSERM U152, Institut Cochin de Génétique Moléculaire, Paris, France.
Sterkers
G
G
Vaquero
C
C
D015152:Blotting, Northern; D015704:CD4 Antigens / Q000235:genetics*; D016827:CD8 Antigens / Q000235:genetics*; D002462:Cell Membrane / Q000276:immunology; D002467:Cell Nucleus / Q000502:physiology; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D015536:Down-Regulation; D005455:Fluorescent Antibody Technique; D006801:Humans; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008222:Lymphokines / Q000235:genetics*; D008957:Models, Genetic; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014158:Transcription, Genetic / Q000187:drug effects*; D015854:Up-Regulation
D015704:CD4 Antigens; D016827:CD8 Antigens; D008222:Lymphokines; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D016572:Cyclosporine; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)