In vivo post-transcriptional regulation of CD154 in mouse CD4⁺ T cells

• Published in: European journal of immunology 2009-08, Vol.39 (8), p.2224-2232
• Main Authors: Vavassori, Stefano, Shi, Yufang, Chen, Chiann-Chyi, Ron, Yacov, Covey, Lori R
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions - genetics; 3' Untranslated Regions - metabolism; Animals; Antibodies, Monoclonal - pharmacology; Antigens - immunology; Base Sequence; CD154; CD28 Antigens - immunology; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD40 Ligand - genetics; Electrophoretic Mobility Shift Assay; Flow Cytometry; Humans; Jurkat Cells; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Mice; Mice, Inbred C57BL; Molecular Sequence Data; mRNA stability; Polypyrimidine Tract-Binding Protein - metabolism; Polypyrimidine tract‐binding protein; Post‐transcriptional regulation; Protein Binding; Reverse Transcriptase Polymerase Chain Reaction; RNA Processing, Post-Transcriptional; RNA Stability; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sequence Homology, Nucleic Acid; Time Factors
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200839163

Interactions between CD40 and its ligand CD154 are involved in the progression of both cell mediated and innate immunity. These interactions are brought about by the transient expression of CD154 on activated CD4⁺ T cells, which is regulated, in part, at the level of mRNA turnover. Here we have focused on analyzing the pattern of post-transcriptional regulation in mouse CD4⁺ T cells in response to activation. Initial experiments identify a region of the murine CD154 mRNA that binds a polypyrimidine tract-binding protein-containing complex (mComplex I), which is activation-dependent and binds to a single CU-rich site within the 3' uTR Subsequent findings demonstrate that in vivo polyclonal activation of T cells leads to a pattern of differential CD154 mRNA stability that is directly dependent on extent of activation. Furthermore, in vitro activation of antigen-primed T cells shows that the CD154 mRNA half-life increases relative to that of unprimed cells. Importantly, this is the first report demonstrating that the regulation of CD154 in vivo is connected to an activation-induced program of mRNA decay and thus provides strong evidence for post-transcriptional mechanisms having a physiological role in regulating CD154 expression during an ongoing immune response.