A Blocking Anti-CD28-Specific Antibody Induces Long-Term Heart Allograft Survival by Suppression of the PKCθ-JNK Signal Pathway
| Autor: | Mei Shiang Jang, Gladys Crews, In Chul Hong, Ogert Fisniku, Laurie Erickson, Masakazu Kobayashi, Fan Pan, K. Tamura, Hongsi Jiang, C. Wynn |
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| Rok vydání: | 2008 |
| Předmět: |
MAP Kinase Kinase 4
T-Lymphocytes T cell chemical and pharmacologic phenomena Lymphocyte Activation Major histocompatibility complex CD28 Antigens Antibody Specificity Rats Inbred BN Blocking antibody medicine Animals Transplantation Homologous Receptor Protein Kinase C PI3K/AKT/mTOR pathway Transplantation biology ZAP70 Graft Survival CD28 hemic and immune systems Rats Cell biology Isoenzymes Transplantation Isogeneic medicine.anatomical_structure Protein Kinase C-theta Rats Inbred Lew Immunology biology.protein Heart Transplantation Signal transduction Signal Transduction |
| Zdroj: | Transplantation. 85:1051-1055 |
| ISSN: | 0041-1337 |
| Popis: | This study investigated the effects of a blocking anti-CD28 antibody (Anti-CD28-PV1-IgG3) in vitro and in vivo. Anti-CD28-PV1-IgG3, a hamster-mouse chimeric antibody against murine CD28, which does not provide CD28-positive signaling during TCR-driven T cell activation, enabled long-term survival of heart allografts across a complete mismatch of the MHC in rats. Among the T cell signaling proteins tested in the spleens from recipients, we found that recipients treated with anti-CD28-PV1-IgG3 exhibited suppression of alloantigen-initiated proximal TCR signaling events, including Lck, Zap70, Vav, and PI3K expression, and their PKC theta- and JNK-regulated expression/activation. This leads to attenuation of intragraft T cell infiltration and expression of T cell effector molecules. These results indicate that targeting the CD28 receptor with a blocking antibody leads to long-term allograft survival by reducing activation of alloantigen-mediated key signaling events in T cells that might be crucial for full T cell activation. |
| Databáze: | OpenAIRE |
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