In vivo post-transcriptional regulation of CD154 in mouse CD4+ T cells.
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.
Vavassori
Stefano
S
Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ, USA.
Shi
Yufang
Y
Chen
Chiann-Chyi
CC
Ron
Yacov
Y
Covey
Lori R
LR
D020413:3' Untranslated Regions / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000941:Antigens / Q000276:immunology; D001483:Base Sequence; D018106:CD28 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D023201:CD40 Ligand / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D038941:Polypyrimidine Tract-Binding Protein / Q000378:metabolism; D011485:Protein Binding; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D013997:Time Factors
D020413:3' Untranslated Regions; D000911:Antibodies, Monoclonal; D000941:Antigens; D018106:CD28 Antigens; D012333:RNA, Messenger; D038941:Polypyrimidine Tract-Binding Protein; D023201:CD40 Ligand