The down-regulation of alpha-interferon receptors in human lymphoblastoid cells: relation to cellular responsiveness to the antiproliferative action of alpha-interferon

Human lymphoblastoid cell lines (Daudi, Daudi subclones, Raji and MOLT-4) were compared for sensitivity to the antiproliferative action of alpha-interferon (IFN-alpha) and down-regulation of IFN-alpha receptors. IFN-sensitive and IFN-resistant cell lines have similar numbers (2-4000/cell) of high affinity (20-75 pM) IFN-alpha receptors. Treatment of IFN-sensitive cells with low concentrations (3-10 pM) of IFN-alpha results in low receptor occupancy and nearly complete (greater than 95%) down-regulation of cell surface IFN-alpha receptors within 5 h. Treatment of resistant cells with higher IFN concentrations (30 pM) only results in partial (approximately 60%) receptor down-regulation that is directly related to receptor occupancy. Receptor-receptor interactions, induced by IFN-alpha binding, may account for the enhanced down-regulation of IFN-alpha receptors in IFN-sensitive cells. Such interactions apparently do not occur in IFN-resistant lymphoblastoid cell lines.