Th1 responsiveness to nephritogenic antigens determines susceptibility to crescentic glomerulonephritis in mice

Kidney Int. 1997 Jan;51(1):94-103. doi: 10.1038/ki.1997.12.


The pattern of glomerulonephritis (GN) developing in response to a planted antigen (sheep anti-mouse GBM globulin) was compared in two strains of mice which demonstrated either a predominant Th1 (C57BL/6) or Th2 (BALB/c) response to this antigen. GN was induced with a subnephritogenic i.v. dose of sheep anti-mouse GBM globulin in mice presensitized to sheep globulin. Sensitized C57BL/6 mice showed pronounced cutaneous delayed-type hypersensitivity (DTH) following the challenge with sheep globulin, low titers of circulating anti-sheep globulin antibody and high interferon gamma (IFN-gamma) and low interleukin 4 (IL-4) production by splenic T cells, consistent with a predominant Th1 pattern of immune response. Sensitized BALB/c mice did not develop DTH following cutaneous challenge with sheep globulin, had higher circulating anti-sheep globulin antibody titers, and showed high IL-4 and low IFN gamma production by splenic T cells compared with C57BL/6 mice, consistent with a predominant Th2 response. In C57BL/6 mice, GN developing in response to sheep globulin exhibited a severe crescentic pattern with prominent glomerular T cell and macrophage influx and fibrin deposition. In vivo depletion with a monoclonal anti-CD4 antibody demonstrated that this injury was T helper cell dependent. Treatment with monoclonal anti-mouse IFN gamma antibody significantly reduced glomerular injury and crescent formation and attenuated the cutaneous DTH response. GN induced by the same protocol in BALB/c mice exhibited pronounced glomerular IgG and complement deposition. Crescent formation, fibrin deposition, and glomerular T cell and macrophage infiltration were significantly less than observed in C57BL/6 mice, and injury was not T cell dependent in the effector phase. These data suggest that the pattern of glomerular injury induced by a planted antigen can be determined by the balance of T helper cell subset activation. A Th1 response induces a severe crescentic pattern of GN, which like cutaneous DTH, is T helper cell and IFN gamma dependent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / immunology
  • Antigens / pharmacology
  • Autoantibodies / immunology
  • CD4 Antigens / immunology
  • Complement System Proteins / analysis
  • Creatinine / blood
  • Creatinine / urine
  • Fibrin / immunology
  • Globulins / immunology
  • Glomerulonephritis / immunology*
  • Glomerulonephritis / pathology
  • Hypersensitivity, Delayed / immunology
  • Immunoglobulin G / immunology
  • Immunoglobulin G / pharmacology
  • Immunoglobulins, Intravenous
  • Interferon-gamma / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Proteinuria
  • Sheep
  • T-Lymphocytes, Helper-Inducer / immunology*


  • Antigens
  • Autoantibodies
  • CD4 Antigens
  • Globulins
  • Immunoglobulin G
  • Immunoglobulins, Intravenous
  • Interferon-gamma
  • Fibrin
  • Complement System Proteins
  • Creatinine