PEST domain-enriched tyrosine phosphatase (PEP) regulation of effector/memory T cells

Science. 2004 Jan 30;303(5658):685-9. doi: 10.1126/science.1092138.

Abstract

Protein tyrosine kinases and phosphatases cooperate to regulate normal immune cell function. We examined the role of PEST domain-enriched tyrosine phosphatase (PEP) in regulating T cell antigen-receptor function during thymocyte development and peripheral T cell differentiation. Although normal naïve T cell functions were retained in pep-deficient mice, effector/memory T cells demonstrated enhanced activation of Lck. In turn, this resulted in increased expansion and function of the effector/memory T cell pool, which was also associated with spontaneous development of germinal centers and elevated serum antibody levels. These results revealed a central role for PEP in negatively regulating specific aspects of T cell development and function.

MeSH terms

  • Animals
  • Autoimmunity
  • B-Lymphocytes / physiology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / physiology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / physiology
  • Cell Cycle
  • Gene Targeting
  • Germinal Center / physiology
  • Hydrogen-Ion Concentration
  • Immunoglobulins / blood
  • Immunologic Memory*
  • Lymphocyte Activation
  • Lymphocyte Count
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Phosphorylation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 12
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / metabolism*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Signal Transduction
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / physiology

Substances

  • Immunoglobulins
  • Receptors, Antigen, T-Cell
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Protein Tyrosine Phosphatase, Non-Receptor Type 12
  • Protein Tyrosine Phosphatases
  • Ptpn12 protein, mouse