title: Predominance of type-2 immune response in idiopathic membranous nephropathy. Cytoplasmic cytokine analysis.
abstract: BACKGROUND
  The Th1/Th2 paradigm is proving increasingly useful in the understanding of infectious diseases and many autoimmune diseases. Th1 cells predominantly produce interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) and are instrumental in initiating delayed-type hypersensitivity and activating macrophages. Th2 cells secrete other cytokines, such as IL-4, IL-5, IL-10 and IL-13 that trigger B-cell activation and immunoglobulin synthesis. It has been shown that in patients with membranous nephropathy, there may be a predominance of Th2, because of the presence of IgG, particularly IgG4, which belongs to a subclass of the type-2 immune response, and complement deposits in glomeruli. In this study, we investigated the immunoresponse of helper T cells, i.e. Th predominance in patients with idiopathic membranous nephropathy.
  
  
  METHODS
  We used flow cytometry to assess the levels of circulating Th cells in patients with idiopathic membranous nephropathy (n = 8) and in normal individuals (n = 23) based on the expression of intracellular type-1 and type-2 cytokines. Because the production of each of these cytokines has a specific time course, we observed the cytokine synthesis at 3, 6, 9 and 12 h after stimulation.
  
  
  RESULTS
  The percentages of IL-2+/CD4+ cells from patients with idiopathic membranous nephropathy were significantly lower than those from normal individuals at 6, 9 and 12 h, with the difference becoming more significant over time. IFN-gamma+/CD4+ cells and IL-4+/CD4+ cells were not significantly different between the two groups. In patients with idiopathic membranous nephropathy, the percentages of IL-10+/CD4+ cells were significantly higher than those in normal individuals at each point in time.
  
  
  CONCLUSIONS
  Increased IL-10-producing Th cells may lead to suppression of delayed-type hypersensitivity and activate suppressor cells and IgG4 synthesis, resulting in idiopathic membranous nephropathy.
authors.affiliation: Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Japan. kidney@md.tsukuba.ac.jp
authors.forename: Kouichi
authors.initials: K
authors.lastname: Hirayama
authors.forename: Itaru
authors.initials: I
authors.lastname: Ebihara
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Hirayasu
authors.initials: H
authors.lastname: Kai
authors.forename: Kaori
authors.initials: K
authors.lastname: Muro
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yamagata
authors.forename: Masaki
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Akio
authors.initials: A
authors.lastname: Koyama
mesh_terms: D000328:Adult; D000368:Aged; D015704:CD4 Antigens / Q000032:analysis; D003593:Cytoplasm / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D015433:Glomerulonephritis, Membranous / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D016753:Interleukin-10 / Q000032:analysis; D007376:Interleukin-2 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000737:chemistry / Q000276:immunology; D018418:Th2 Cells / Q000737:chemistry / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D007074:Immunoglobulin G; D007376:Interleukin-2; D016753:Interleukin-10