Regulation of CD154 (CD40 ligand) mRNA stability during T cell activation.
The CD154 protein (CD40 ligand), which is critical to the regulation of both humoral and cellular immune responses, is expressed transiently on the surface of activated CD4+ T cells. To determine whether control of mRNA stability contributes to the highly regulated expression of CD154 during T cell activation, CD4+ T cells were isolated from human peripheral blood and stimulated for various lengths of time with plate-bound anti-CD3 mAb. At early times after anti-CD3 activation, the CD154 message was found to be very unstable, however, the stability measurably increased after 24-48 h of activation. Similar analyses of TNF-alpha and c-myc mRNA decay throughout a time course of T cell activation revealed patterns of regulation that were distinct from CD154. Similar to the effect on TNF-alpha mRNA, stimulation of T cells with PMA + ionomycin greatly increased the stability of CD154 message. However, CD154 message stability was only modestly increased in T cells coactivated with anti-CD3 and anti-CD28 at 5 h and not increased by costimulation at 24 h. Finally, an analysis of both mRNA and surface protein expression over a time course of T cell activation with anti-CD3 revealed a rapid induction of expression early after activation. This induction was followed by a more gradual decrease in expression over the next 48 h. Together, these data support a role for posttranscriptional regulation in the control and overall expression of CD154 in activated T cells.
Ford
G S
GS
Division of Life Sciences, Rutgers, The State University of New Jersey, Piscataway 08854, USA.
Barnhart
B
B
Shone
S
S
Covey
L R
LR
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018106:CD28 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D023201:CD40 Ligand; D002478:Cells, Cultured; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006207:Half-Life; D006801:Humans; D007477:Ions; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D007477:Ions; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D013755:Tetradecanoylphorbol Acetate