ALTERED SYNTHESIS OF INTERFERON-GAMMA AND EXPRESSION OF INTERFERON-GAMMA RECEPTOR BY PERIPHERAL-BLOOD MONONUCLEAR-CELLS FROM PATIENTS WITH IGA NEPHROPATHY AND NON-IGA PROLIFERATIVE GLOMERULONEPHRITIS

Previously we reported disease-specific interaction between interferon -gamma (IFN-gamma) and interleukin-4 (IL-4) in patients with IgA nephr opathy (IgAN), suggesting the existence of unusual T cell behavior in this disease. In the present study, we investigated characteristic syn thesis of interferon-gamma (IFN-gamma) and expression of IFN-gamma rec eptor (IFN-gamma R) in the peripheral blood mononuclear cells (PBMC) f rom patients with IgAN and other chronic proliferative glomerulonephri tis (PGN). Heparinized peripheral blood samples were obtained from 38 patients with chronic mesangial proliferative glomerulonephritis (CGN; including 24 with IgA nephropathy) and 20 healthy controls. PBMC were isolated by gradient centrifugation and fragments were cultured in Is cove's modified Dulbecco's medium (IMDM) supplemented with 10% fetal c alf serum (FCS) for 72 hr. IFN-gamma concentrations in supernatants we re evaluated by the enzyme-linked immunosorbent assay (ELISA). Other p arts of PBMC pellets were reacted with anti-human IFN-gamma R monoclon al antibody and FITC-labeled anti-mouse second antibody for analysis o f IFN-gamma R expression on these cells by FACScan. The remaining PBMC were fractionated into CD4(+) T cells, CD8(+) T cells, B cells, NK, c ells and macrophages using the MACS cell sorting system. The isolated cells were evaluated for IFN-gamma or IFN-gamma R mRNA expression by t he semiquantitative RT-PCR method. In vitro IFN-gamma synthesis was en hanced in patients with CGN, and NK cells were revealed to be responsi ble for such enhancement. On the other hand, the expression of IFN-gam ma R on macrophages was suppressed in CGN patients. These results sugg est that impairment of regulation of the IFN-gamma system might be inv olved in the development of CGN.