Monoclonal antibody-assisted stimulation of adenosine A2A receptors induces simultaneous downregulation of CXCR4 and CCR5 on CD4+ T-cells.
Immunocompetent cells express various G-protein-coupled receptors that transduce extracellular signals across the plasma membrane. Among them, CXCR4 and CCR5 chemokines receptors and adenosine A(2A) receptors (A(2A)R) are involved in inflammatory processes. Considering that A(2A)R activation may have incidence on CXCR4 and CCR5 protein expression through heterologous desensitization process, we tested Adonis, an agonist-like monoclonal antibody to A(2A)R on CD4+ CEM T-cells. We found that Adonis inhibited the CEM cell growth, upregulated A(2A)R and downregulated CXCR4 and CCR5 without modifying the CD4 expression. By reducing the expression of CXCR4 and CCR5 chemokines receptors utilized as entry co-receptors by HIV-1 during viral infection of CD4 expressing cells, Adonis stimulation of A(2A)R appears as a valuable means to treat infected cells.
By
Youlet
Y
UMR MD2 P2COE, Université de la Méditerranée, Faculté de Médecine, Marseille, France.
Durand-Gorde
Josée-Martine
JM
Condo
Jocelyne
J
Lejeune
Pierre-Jean
PJ
Fenouillet
Emmanuel
E
Guieu
Régis
R
Ruf
Jean
J
D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D006801:Humans; D043705:Receptor, Adenosine A2A / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D019713:Receptors, CCR5 / Q000096:biosynthesis / Q000235:genetics; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction
D058908:Adenosine A2 Receptor Agonists; D000911:Antibodies, Monoclonal; C527276:CXCR4 protein, human; D043705:Receptor, Adenosine A2A; D019713:Receptors, CCR5; D019718:Receptors, CXCR4