Journal article
CD5 Costimulation Up-Regulates the Signaling to Extracellular Signal-Regulated Kinase Activation in CD4+CD8+ Thymocytes and Supports Their Differentiation to the CD4 Lineage
The Journal of immunology (1950), v 164(3), pp 1260-1268
01 Feb 2000
PMID: 10640739
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Abstract 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.
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Details
- Title
- CD5 Costimulation Up-Regulates the Signaling to Extracellular Signal-Regulated Kinase Activation in CD4+CD8+ Thymocytes and Supports Their Differentiation to the CD4 Lineage
- Creators
- Xu-Yu ZhouYumi Yashiro-Ohtani - The University of OsakaKazuhito Toyo-oka - The University of OsakaCheung-Seog Park - The University of OsakaXu-Guang TaiToshiyuki Hamaoka - The University of OsakaHiromi Fujiwara - The University of Osaka
- Publication Details
- The Journal of immunology (1950), v 164(3), pp 1260-1268
- Publisher
- American Association of Immunologists (AAI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000084910300017
- Scopus ID
- 2-s2.0-0034141530
- Other Identifier
- 991020100077004721
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- Web of Science research areas
- Immunology