Modulation of interferon-alpha and interferon-gamma receptor expression during T-lymphocyte activation and proliferation.
Freshly isolated normal human T lymphocytes constitutively expressed receptors for interferon-alpha (IFN-alpha) and IFN-gamma. Upon activation, the number of IFN-alpha receptors increased, paralleling the increases in cell size to give a nearly constant density of IFN-alpha receptors. In contrast, activation of T lymphocytes with phytohemagglutinin (PHA), concanavalin A (ConA), or phorbol myristate acetate (PMA) for 18 h decreased the specific binding of radiolabeled [Cys-Tyr-Cys] rIFN-gamma to acid-washed cells. Scatchard analysis demonstrated that the decreased binding was due to a reduction in the number of high affinity IFN-gamma receptors. Moreover, resting T lymphocytes had a single class of high-affinity IFN-gamma receptors, whereas the activated cells appeared to have both high- and lower-affinity IFN-gamma binding sites. When normalized for differences in cell size, the number of high-affinity IFN-gamma receptors per unit cell surface area was approximately twofold lower on activated than on resting T lymphocytes. At least part of the decrease was due to receptor downregulation by endogenously produced IFN-gamma, since monoclonal antibodies to IFN-gamma prevented a large portion of the PHA-induced decrease in IFN-gamma receptors.
D000143:Acids / Q000494:pharmacology; D001667:Binding, Competitive; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007457:Iodine Radioisotopes; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D010835:Phytohemagglutinins / Q000494:pharmacology; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000502:physiology*; D017471:Receptors, Interferon; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000648:ultrastructure*
D000143:Acids; D007370:Interferon Type I; D007457:Iodine Radioisotopes; D010835:Phytohemagglutinins; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D007371:Interferon-gamma; C052220:interferon gamma, Cys(-3), Tyr(-2), Cys(-1)-