CTLA-4-Mediated inhibition of early events of T cell proliferation
| Autor: | M C, Brunner, C A, Chambers, F K, Chan, J, Hanke, A, Winoto, J P, Allison |
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| Rok vydání: | 1999 |
| Předmět: |
CD4-Positive T-Lymphocytes
Immunoconjugates CD3 Complex Transcription Genetic Cell Cycle Proteins Mice Transgenic Protein Serine-Threonine Kinases Lymphocyte Activation Abatacept Mice CD28 Antigens Antigens CD Genes Reporter Cyclins Proto-Oncogene Proteins Animals Humans CTLA-4 Antigen RNA Messenger Cyclin D3 S-Phase Kinase-Associated Proteins NFATC Transcription Factors Tumor Suppressor Proteins Cell Cycle Cyclin-Dependent Kinase 4 Nuclear Proteins Biological Transport Cyclin-Dependent Kinase 6 Antigens Differentiation Cyclin-Dependent Kinases DNA-Binding Proteins Interleukin-2 Microtubule-Associated Proteins Cyclin-Dependent Kinase Inhibitor p27 Immunosuppressive Agents Transcription Factors |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 162(10) |
| ISSN: | 0022-1767 |
| Popis: | CTLA-4 engagement by mAbs inhibits, while CD28 enhances, IL-2 production and proliferation upon T cell activation. Here, we have analyzed the mechanisms involved in CTLA-4-mediated inhibition of T cell activation of naive CD4+ T cells using Ab cross-linking. CTLA-4 ligation inhibited CD3/CD28-induced IL-2 mRNA accumulation by inhibiting IL-2 transcription, which appears to be mediated in part through decreasing NF-AT accumulation in the nuclei. However, CTLA-4 ligation did not appear to affect the CD28-mediated stabilization of IL-2 mRNA. Further, CTLA-4 engagement inhibited progression through the cell cycle by inhibiting the production of cyclin D3, cyclin-dependent kinase (cdk)4, and cdk6 when the T cells were stimulated with anti-CD3/CD28 and with anti-CD3 alone. These results indicate that CTLA-4 signaling inhibits events early in T cell activation both at IL-2 transcription and at the level of IL-2-independent events of the cell cycle, and does not simply oppose CD28-mediated costimulation. |
| Databáze: | OpenAIRE |
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