CD5 costimulation up-regulates the signaling to extracellular signal-regulated kinase activation in CD4+CD8+ thymocytes and supports their differentiation to the CD4 lineage

J Immunol. 2000 Feb 1;164(3):1260-8. doi: 10.4049/jimmunol.164.3.1260.


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-gamma (PLC-gamma) compared with ligation with anti-CD3 alone. Despite increased phosphorylation of PLC-gamma, 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / metabolism
  • CD3 Complex / immunology
  • CD3 Complex / metabolism
  • CD4 Antigens / biosynthesis
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / enzymology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD5 Antigens / immunology
  • CD5 Antigens / metabolism
  • CD5 Antigens / physiology*
  • CD8 Antigens / biosynthesis
  • Calcium / immunology
  • Calcium / metabolism
  • Cell Differentiation / immunology
  • Cell Lineage / immunology
  • Enzyme Activation / immunology
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • Ligands
  • Mice
  • Mice, Inbred BALB C
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism*
  • Mitogen-Activated Protein Kinases / physiology
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Receptors, Antigen, T-Cell / physiology
  • Signal Transduction / immunology*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / enzymology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Thymus Gland / cytology
  • Up-Regulation / immunology*


  • Antibodies, Monoclonal
  • CD3 Complex
  • CD4 Antigens
  • CD5 Antigens
  • CD8 Antigens
  • Enzyme Inhibitors
  • Flavonoids
  • Ligands
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Antigen, T-Cell
  • Mitogen-Activated Protein Kinases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
  • Calcium