Cyclo-oxygenase type 2-dependent prostaglandin E2 secretion is involved in retrovirus-induced T-cell dysfunction in mice.
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.
Rahmouni
Souad
S
Department of Pathology, University of Liège, B-4000 Liège, Belgium.
Aandahl
Einar Martin
EM
Nayjib
Btissam
B
Zeddou
Mustapha
M
Giannini
Sandra
S
Verlaet
Myriam
M
Greimers
Roland
R
Boniver
Jaques
J
Tasken
Kjetil
K
Moutschen
Michel
M
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000821:virology; D039481:CD11b Antigen / Q000032:analysis / Q000378:metabolism; D017635:Clonal Anergy; D000242:Cyclic AMP / Q000378:metabolism; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D004790:Enzyme Induction; D006678:HIV / Q000276:immunology / Q000472:pathogenicity; D008198:Lymph Nodes / Q000166:cytology / Q000201:enzymology / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D016721:Radiation Leukemia Virus / Q000472:pathogenicity / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000821:virology*
D039481:CD11b Antigen; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D043562:Receptors, G-Protein-Coupled; D000242:Cyclic AMP; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D015232:Dinoprostone