Transcriptional and post-transcriptional regulation of TcR, CD4 and CD8 gene expression during activation of normal human T lymphocytes.
We previously showed that the turnover rates of the messengers coding for the T cell receptor (TcR) alpha, beta and gamma, CD4 and CD8 molecules composing the multireceptor complex vary in normal human mature T lymphocytes according to their state of activation. Activation by soluble anti-CD3 which does not induce proliferation, promotes a weak up-modulation of the corresponding five mRNAs. In contrast, activation signals such as anti-CD3 + PMA, which lead to lymphokine mRNA expression and T cell proliferation, promote a decrease of the TcR, CD4 and CD8 mRNA levels within 4 h post-activation, followed by their gradual re-expression. Here we show that the down-modulation of these mRNAs results from early regulation controls at transcriptional and post-transcriptional levels, i.e. through a concomitant inhibition of transcription and destabilization of the mRNA. Moreover, later re-expression of the mRNA results from recovery of transcription and marked increase of the mRNA stability. Finally, down-modulation is specific for TcR, CD4 and CD8 mRNAs, all submitted to similar regulation processes. These results strongly suggest a direct correlation between down-modulation of the multireceptor complex mRNAs, and lymphokine mRNA expression, and cellular proliferation.
Paillard
F
F
Laboratoire d'Immunologie et Oncologie des Maladies Rétrovirales, INSERM U 152, CNRS URA 628, Hôpital Cochin, Paris, France.
Sterkers
G
G
Vaquero
C
C
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics* / Q000276:immunology; D017252:CD3 Complex; D015704:CD4 Antigens / Q000235:genetics*; D016827:CD8 Antigens; D002478:Cells, Cultured; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D012333:RNA, Messenger / Q000096:biosynthesis*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D013755:Tetradecanoylphorbol Acetate