Immune interferon induces early and late events in differentiation of HL-60 cells that are part of the same maturation program.

It has been shown that 37% of the bulk HL-60 cell population is induced by immune interferon (IFN) to express functional colony-stimulating factor-1 (CSF-1) receptors. A 2-day treatment with IFN sets in motion a differentiation program that leads to an early and transient increase of human leukocyte antigen-DR (HLA-DR) and a delayed appearance of CSF-1 receptors. In this study we have investigated the inverse relationship between class II and CSF-1 receptor expression and found that IFN acts only on an IFN-sensitive HL-60 cell population that is class II negative. This population becomes susceptible to induction and expresses the early HLA-DR surface antigen. The same cells become programmed to acquire CSF-1 receptors at a later time, an effect that cannot be substituted by another agent (A23187) known to have the same effect as IFN on DR expression. Induced class II expression by itself is not sufficient to predict a future CSF-1 receptor appearance, suggesting that HLA-DR induction by IFN is an accompanying rather than a causative event, although inhibition of class II expression completely ablates the IFN up-regulation of CSF-1 receptors. In contrast, constitutive class II-positive HL-60 cells do not respond to CSF-1, nor they can be induced to do so.