Cyclo-oxygenase type 2-dependent prostaglandin E2 secretion is involved in retrovirus-induced T-cell dysfunction in mice

Biochem J. 2004 Dec 15;384(Pt 3):469-76. doi: 10.1042/BJ20031859.

Abstract

MAIDS (murine AIDS) is caused by infection with the murine leukaemia retrovirus RadLV-Rs and is characterized by a severe immunodeficiency and T-cell anergy combined with a lymphoproliferative disease affecting both B- and T-cells. Hyperactivation of the cAMP-protein kinase A pathway is involved in the T-cell dysfunction of MAIDS and HIV by inhibiting T-cell activation through the T-cell receptor. In the present study, we show that MAIDS involves a strong and selective up-regulation of cyclo-oxygenase type 2 in the CD11b+ subpopulation of T- and B-cells of the lymph nodes, leading to increased levels of PGE2 (prostaglandin E2). PGE2 activates the cAMP pathway through G-protein-coupled receptors. Treatment with cyclo-oxygenase type 2 inhibitors reduces the level of PGE2 and thereby reverses the T-cell anergy, restores the T-cell immune function and ameliorates the lymphoproliferative disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / virology
  • CD11b Antigen / analysis
  • CD11b Antigen / metabolism
  • Clonal Anergy
  • Cyclic AMP / metabolism
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology
  • Dinoprostone / antagonists & inhibitors
  • Dinoprostone / biosynthesis
  • Dinoprostone / metabolism*
  • Enzyme Induction
  • HIV / immunology
  • HIV / pathogenicity
  • Lymph Nodes / cytology
  • Lymph Nodes / enzymology
  • Lymph Nodes / immunology
  • Lymph Nodes / virology
  • Lymphocyte Activation
  • Male
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Murine Acquired Immunodeficiency Syndrome / immunology
  • Murine Acquired Immunodeficiency Syndrome / metabolism
  • Murine Acquired Immunodeficiency Syndrome / pathology
  • Murine Acquired Immunodeficiency Syndrome / virology
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Radiation Leukemia Virus / pathogenicity
  • Radiation Leukemia Virus / physiology*
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology*
  • T-Lymphocytes / virology*

Substances

  • CD11b Antigen
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Membrane Proteins
  • Receptors, G-Protein-Coupled
  • Cyclic AMP
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Ptgs1 protein, mouse
  • Dinoprostone