CD5 Costimulation Up-Regulates the Signaling to Extracellular Signal-Regulated Kinase Activation in CD4+CD8+ Thymocytes and Supports Their Differentiation to the CD4 Lineage
| Autor: | Hiromi Fujiwara, Xuyu Zhou, Kazuhito Toyo-oka, Yumi Yashiro-Ohtani, Xu-Guang Tai, Toshiyuki Hamaoka, Cheung-Seog Park |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
CD4-Positive T-Lymphocytes
CD3 Complex CD8 Antigens CD3 Immunology Population Receptors Antigen T-Cell Linker for Activation of T cells chemical and pharmacologic phenomena Thymus Gland Biology CD5 Antigens Ligands Mice chemistry.chemical_compound T-Lymphocyte Subsets Animals Immunology and Allergy Cell Lineage Enzyme Inhibitors Protein kinase A education Flavonoids Mice Inbred BALB C education.field_of_study Kinase Antibodies Monoclonal Cell Differentiation hemic and immune systems Tyrosine phosphorylation Up-Regulation Cell biology Enzyme Activation Proto-Oncogene Proteins c-bcl-2 chemistry CD4 Antigens biology.protein Phosphorylation Calcium Mitogen-Activated Protein Kinases CD8 Signal Transduction |
| Zdroj: | The Journal of Immunology. 164:1260-1268 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.164.3.1260 |
| Popis: | CD5 positively costimulates TCR-stimulated mature T cells, whereas this molecule has been suggested to negatively regulate the activation of TCR-triggered thymocytes. We investigated the effect of CD5 costimulation on the differentiation of CD4+CD8+ thymocytes. Coligation of thymocytes with anti-CD3 and anti-CD5 induced enhanced tyrosine phosphorylation of LAT (linker for activation of T cells) and phospholipase C-γ (PLC-γ) compared with ligation with anti-CD3 alone. Despite increased phosphorylation of PLC-γ, this treatment down-regulated Ca2+ influx. In contrast, the phosphorylation of LAT and enhanced association with Grb2 led to activation of extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase. When CD3 and CD5 on CD4+CD8+ thymocytes in culture were coligated, they lost CD8, down-regulated CD4 expression, and induced CD69 expression, yielding a CD4+(dull)CD8−CD69+ population. An ERK inhibitor, PD98059, inhibited the generation of this population. The reduction of generation of CD4+CD8− cells resulted from decreased survival of these differentiating thymocytes. Consistent with this, PD98059 inhibited the anti-CD3/CD5-mediated Bcl-2 induction. These results indicate that CD5 down-regulates a branch of TCR signaling, whereas this molecule functions to support the differentiation of CD4+CD8+ thymocytes by up-regulating another branch of TCR signaling that leads to ERK activation. |
| Databáze: | OpenAIRE |
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