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.
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.
Fedoseyeva
E V
EV
Department of Surgery, University of California, San Francisco 94143-0508.
Li
Y
Y
Huey
B
B
Tam
S
S
Hunt
C A
CA
Benichou
G
G
Garovoy
M R
MR
D000938:Antigen-Presenting Cells / Q000276:immunology; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D005802:Genes, MHC Class II; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000037:antagonists & inhibitors*; D007375:Interleukin-1 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D007375:Interleukin-1; D009838:Oligodeoxyribonucleotides; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma