title: Kinetics of adaptive immunity to cationic bovine serum albumin-induced membranous nephropathy.
abstract: Membranous nephropathy is an autoimmune-mediated glomerulonephritis and a major cause of nephrotic syndrome. We studied the kinetics of adaptive immunity in the pathogenesis of membranous nephropathy in T1/T2 double transgenic mice (T1/T2 TG mice) that express human Thy1 protein under the control of interferon-gamma (INF-gamma) and mouse Thy1.1 protein under the control of interleukin (IL)-4. Nephropathy was induced by cationic bovine serum albumin. We found that splenocytes expressed a progressive Th2 response and a subsequent compensatory T-helper 1 (Th1) response, with a gradual augmentation of IL-4-producing Th2 cells and INF-gamma-producing Th1 cells. Increased Th2 marker expression was seen in peripheral blood and kidney cells, with the immunoglobulin G1 (IgG1) antibody isotype predominant in the serum and kidneys. We found that CD8+ T cells contribute more to the augmented INF-gamma production than CD4+ T cells. Moreover, CD19+ B cells demonstrated a greater production of IL-4 than the CD4+ T cells. Cytokine-related gene expression in kidneys and splenocytes showed an upregulation of proinflammatory Th1 and Th2 cytokines. Th2 cells but not Th1 cells were significantly correlated with serum cholesterol and proteinuria. Our study shows that both peripheral and renal immune reactions are strongly polarized toward Th2-type immune responses during the course of membranous nephropathy. The T1/T2 mouse model may help decipher the kinetic changes of adaptive immunity in glomerulonephritis.
authors.affiliation: Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan.
authors.forename: C-C
authors.initials: CC
authors.lastname: Wu
authors.forename: J-S
authors.initials: JS
authors.lastname: Chen
authors.forename: S-J
authors.initials: SJ
authors.lastname: Chen
authors.forename: S-H
authors.initials: SH
authors.lastname: Lin
authors.forename: A
authors.initials: A
authors.lastname: Chen
authors.forename: L-C
authors.initials: LC
authors.lastname: Chang
authors.forename: H-K
authors.initials: HK
authors.lastname: Sytwu
authors.forename: Y-F
authors.initials: YF
authors.lastname: Lin
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007668:Kidney / Q000276:immunology / Q000378:metabolism; D007700:Kinetics; D008213:Lymphocyte Activation / Q000502:physiology; D016131:Lymphocyte Subsets / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D012710:Serum Albumin, Bovine; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*; D018800:Thy-1 Antigens / Q000235:genetics / Q000378:metabolism*
chemical_list: D007136:Immunoglobulins; D012333:RNA, Messenger; D018800:Thy-1 Antigens; D015847:Interleukin-4; D012710:Serum Albumin, Bovine; D007371:Interferon-gamma