Interferon induction in human mixed leukocyte-tumor-cell reactions: evidence for restriction to a certain lineage expressing glycophorin A.

This study reports the induction of interferon (IFN) in human mononuclear cells (MNC) by hematopoietic tumor cells. Only 3 out of 15 cell lines were capable of inducing IFN in the mixed leukocyte/tumor-cell reaction (MLTR). K562, a pluripotent stem cell line and DUTKO-I, a hybrid between K562 and Daudi (Burkitt lymphoma) induced high levels of antiviral activity (ranging from 50-440 units IFN/ml). PUTKO-I, a hybrid between K562 and P3HR-I (Burkitt lymphoma) induced very low levels of IFN (10 units/ml). This antiviral activity was produced by HLA-DR + adherent cells as revealed by different cell separation techniques, and shared well-known properties of IFN gamma (isoelectric point, inactivation by anti-human IFN gamma antibodies; species-restricted protection). MLTR-induced IFN induction could be blocked by enzyme treatment of tumor cells, but was still present when glutaraldehyde-fixed cells were used for induction. Analysis of the cells by flow cytometry for expression of glycophorin A (GpA) revealed that expression of GpA correlated with the ability to induce antiviral activity in MLTR. Furthermore, isolated GpA could be used as a stimulant as well and the response to either K562 cells or soluble GpA was enhanced up to ten-fold by the addition of a GpA-specific monoclonal antibody.