INHIBITION OF INTERFERON-GAMMA-MEDIATED IMMUNE FUNCTIONS BY OLIGONUCLEOTIDES - SUPPRESSION OF HUMAN T-CELL PROLIFERATION BY DOWN-REGULATIONOF IFN-GAMMA-INDUCED ICAM-1 AND FC-RECEPTOR ON ACCESSORY CELLS

Recent progress in gene therapy may provide a new strategy for prevent ion of allograft rejection. Oligonucleotides have been shown to inhibi t specific gene transcription in both cell-free and living-cell system s. In our previous studies, a 26-mer oligonucleotide (T2) designed to form a triple helix with the X/X2 box promoter region of human MRC cla ss II (DRA) gene was shown to prevent the induction by IFN gamma of HL A-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 e ffect on TNF alpha- and IL-l-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 a ssessed by Bow cytometry. Furthermore, pretreatment of monocytes with T2 resulted in suppression of anti-CD3-mediated peripheral blood T cel l proliferation. The presented data suggest that oligonucleotide T2 bl ockade of IFN gamma-induction of different immune receptors on accesso ry cells is associated with inhibition of T cell proliferative respons es.