Immunoregulatory functions of paf-acether. III. Down-regulation of CD4+ T cells high-affinity IL-2 receptor expression.
In the present report, we further explored the mechanisms by which 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (paf-acether), a phospholipid mediator of inflammation inhibited PHA-induced CD4+ cell proliferation. Evidence was obtained that CD4+ cells stimulated with either PHA or immobilized OKT3 in the presence of paf at concentrations that block CD4+ cell proliferation, exhibited a marked decrease in high affinity IL-2R expression. Importantly, paf did not prevent the binding of IL-2 to its receptor. Scatchard analysis of the binding data indicated that paf caused more than 50% decrease in the number of IL-2 high affinity sites per cell, whereas the receptor ligand affinity remained essentially constant. Moreover, the down-regulation of high affinity IL-2R was also accompanied by a loss of IL-2-dependent proliferative capacity. Together these data suggest that decreased expression of high affinity IL-2R may contribute to the diminished proliferative activity observed in CD4+ cells stimulated with PHA or immobilized OKT3 in the presence of paf. They further emphasize the potential role of lipid proinflammatory mediators such as paf in the regulation of T cell activation.
Dulioust
A
A
INSERM U 200, Université Paris-Sud, 32 rue des Carnets, Clamart, France.
Duprez
V
V
Pitton
C
C
Salem
P
P
Hemar
A
A
Benveniste
J
J
Thomas
Y
Y
D015703:Antigens, CD / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D015536:Down-Regulation; D006649:Histocompatibility Antigens / Q000032:analysis; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation; D010835:Phytohemagglutinins / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D013997:Time Factors
D015703:Antigens, CD; D000943:Antigens, Differentiation; D015704:CD4 Antigens; D006649:Histocompatibility Antigens; D007376:Interleukin-2; D010835:Phytohemagglutinins; D010972:Platelet Activating Factor; D015375:Receptors, Interleukin-2; D017493:Leukocyte Common Antigens