Regulation of CD154 (CD40 Ligand) mRNA Stability During T Cell Activation

• Published in: The Journal of immunology (1950) 1999-04, Vol.162 (7), p.4037-4044
• Main Authors: Ford, Gregory S, Barnhart, Bryan, Shone, Scott, Covey, Lori R
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal - pharmacology; CD28 Antigens - immunology; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD40 Ligand; Cells, Cultured; Flow Cytometry; Gene Expression Regulation - drug effects; Gene Expression Regulation - immunology; Half-Life; Humans; Ions; Kinetics; Lymphocyte Activation - drug effects; Lymphocyte Activation - genetics; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; RNA, Messenger - metabolism; Tetradecanoylphorbol Acetate - pharmacology; Transcription, Genetic - immunology; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Up-Regulation - drug effects; Up-Regulation - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.162.7.4037

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.