Inhibition of interferon-gamma-mediated immune functions by oligonucleotides. Suppression of human T cell proliferation by downregulation of IFN-gamma-induced ICAM-1 and Fc-receptor on accessory cells

Abstract

Recent progress in gene therapy may provide a new strategy for prevention of allograft rejection. Oligonucleotides have been shown to inhibit specific gene transcription in both cell-free and living-cell systems. In our previous studies, a 26-mer oligonucleotide (T2) designed to form a triple helix with the X/X2 box promoter region of human MHC class II (DRA) gene was shown to prevent the induction by IFN-gamma of HLA-DR molecules. Here, we show that this oligonucleotide downregulates two other IFN gamma-inducible molecules, the adhesion molecule ICAM-1 and the Fc receptor for IgG on the surface of human cells. T2 has no effect on TNF alpha- and IL-1-mediated ICAM-1 upregulation, showing its specificity for IFN gamma. T2 oligonucleotide is shown to inhibit IFN gamma-mediated induction of Fc receptor on human blood monocytes as assessed by flow cytometry. Furthermore, pretreatment of monocytes with T2 resulted in suppression of anti-CD3-mediated peripheral blood T cell proliferation. The presented data suggest that oligonucleotide T2 blockade of IFN gamma-induction of different immune receptors on accessory cells is associated with inhibition of T cell proliferative responses.