Down-regulation of the interferon receptor.

The binding of 125I-labeled alpha A interferon to human lymphoblastoid Daudi cells decreased when these cells were incubated with unlabeled alpha or beta interferon. This decrease could not be accounted for by the occupancy of interferon receptors with unlabeled interferon and it apparently resulted from the loss or down-regulation of receptors. The binding activity gradually increased when Daudi cells were incubated in fresh medium after a treatment with interferon, but inhibition of protein synthesis with cycloheximide prevented this recovery. Treatment of Daudi cells with this inhibitor resulted in the loss of half the interferon binding activity within 5 h. These findings suggested that the interferon receptors turn over at a basal rate in interferon-free medium and at an increased rate in cells incubated with interferon. The dose-response for the down-regulation was investigated by treating Daudi cells with different concentrations of alpha interferon. Down-regulation was observed in cells treated with relatively low doses of interferon, sufficient to elicit a biological response. The synthesis of the enzyme (2',5')oligo(A) polymerase was induced at the lowest interferon concentrations tested which caused receptor down-regulation.