Journal of the American Society of Nephrology
2007 JASN IMPACT FACTOR 7.111 HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP 
    advanced
CURRENT ISSUE ARCHIVES JASN Express ONLINE SUBMISSION


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by KITCHING, A. R.
Right arrow Articles by TIPPING, P. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by KITCHING, A. R.
Right arrow Articles by TIPPING, P. G.
J Am Soc Nephrol 10:752-759, 1999
© 1999 American Society of Nephrology

REGULAR ARTICLES

IFN-{gamma} Mediates Crescent Formation and Cell-Mediated Immune Injury in Murine Glomerulonephritis

A. RICHARD KITCHING, STEPHEN R. HOLDSWORTH and PETER G. TIPPING

Centre for Inflammatory Diseases, Monash University, Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia.

Correspondence to Dr. A. Richard Kitching, Monash University Department of Medicine, Monash Medical Centre, 246 Clayton Road, Clayton 3168, Victoria, Australia. Phone: 61 3 9550 5543; Fax: 61 3 9550 5524; E-mail: richard.kitching{at}med.monash.edu.au

Abstract. Features of crescentic glomerulonephritis suggest that it results from a T helper 1 (Th1) nephritogenic immune response. Interferon-{gamma} (IFN-{gamma}), produced by Th1 cells, is involved in T cell-directed macrophage activation in effector Th1 responses. The hypothesis that endogenous IFN-{gamma} contributes to the development of crescentic glomerulonephritis was tested by comparing the development of glomerulonephritis (induced by a planted antigen) and immune responses in normal C57BL/6 mice (IFN-{gamma} +/+) and in mice genetically deficient in IFN-{gamma} (IFN-{gamma} -/-). Ten days after the initiation of glomerulonephritis, IFN-{gamma} -/- mice developed fewer glomerular crescents (5 ± 1% versus 26 ± 3%, P < 0.005), less severe glomerular injury, and less renal impairment. Effectors of delayed-type hypersensitivity (CD4+ T cells, macrophages, and fibrin) in glomeruli were reduced in IFN-{gamma} -/- mice. Skin delayed-type hypersensitivity to sheep globulin was reduced. Total antigen-specific Ig and splenocyte interleukin-2 production were unchanged, but antigen-specific serum IgG2a was reduced. Markers of an antigen-specific Th2 response (serum IgG1, splenocyte interleukin-4) were unchanged. Studies 22 d after the initiation of glomerulonephritis showed that IFN-{gamma} -/- mice still had fewer crescents (11 ± 2% versus 22 ± 3%, P = 0.02) and glomerular CD4+ T cells and macrophages than IFN-{gamma} +/+ mice. These studies demonstrate that endogenous IFN-{gamma} mediates crescentic glomerulonephritis by promoting cell-mediated immune injury. They support the hypothesis that crescentic glomerulonephritis is a manifestation of a Th1 nephritogenic immune response.




This article has been cited by other articles:


Home page
 J. Am. Soc. Nephrol.Home page
R. K. S. Phoon, A. R. Kitching, D. Odobasic, L. K. Jones, T. J. Semple, and S. R. Holdsworth
T-bet Deficiency Attenuates Renal Injury in Experimental Crescentic Glomerulonephritis
J. Am. Soc. Nephrol., March 1, 2008; 19(3): 477 - 485.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
J. Scholz, V. Lukacs-Kornek, D. R. Engel, S. Specht, E. Kiss, F. Eitner, J. Floege, H.-J. Groene, and C. Kurts
Renal Dendritic Cells Stimulate IL-10 Production and Attenuate Nephrotoxic Nephritis
J. Am. Soc. Nephrol., March 1, 2008; 19(3): 527 - 537.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. Menke, J. A. Lucas, G. C. Zeller, M. E. Keir, X. R. Huang, N. Tsuboi, T. N. Mayadas, H. Y. Lan, A. H. Sharpe, and V. R. Kelley
Programmed Death 1 Ligand (PD-L) 1 and PD-L2 Limit Autoimmune Kidney Disease: Distinct Roles
J. Immunol., December 1, 2007; 179(11): 7466 - 7477.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
U. Panzer, O. M. Steinmetz, H.-J. Paust, C. Meyer-Schwesinger, A. Peters, J.-E. Turner, G. Zahner, F. Heymann, C. Kurts, H. Hopfer, et al.
Chemokine Receptor CXCR3 Mediates T Cell Recruitment and Tissue Injury in Nephrotoxic Nephritis in Mice
J. Am. Soc. Nephrol., July 1, 2007; 18(7): 2071 - 2084.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
D. Odobasic, A. R. Kitching, T. J. Semple, and S. R. Holdsworth
Endogenous Myeloperoxidase Promotes Neutrophil-Mediated Renal Injury, but Attenuates T Cell Immunity Inducing Crescentic Glomerulonephritis
J. Am. Soc. Nephrol., March 1, 2007; 18(3): 760 - 770.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
A.-J. Ruth, A. R. Kitching, R. Y.Q. Kwan, D. Odobasic, J. D.K. Ooi, J. R. Timoshanko, M. J. Hickey, and S. R. Holdsworth
Anti-Neutrophil Cytoplasmic Antibodies and Effector CD4+ Cells Play Nonredundant Roles in Anti-Myeloperoxidase Crescentic Glomerulonephritis
J. Am. Soc. Nephrol., July 1, 2006; 17(7): 1940 - 1949.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. P. Kuligowski, A. R. Kitching, and M. J. Hickey
Leukocyte Recruitment to the Inflamed Glomerulus: A Critical Role for Platelet-Derived P-Selectin in the Absence of Rolling.
J. Immunol., June 1, 2006; 176(11): 6991 - 6999.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
P. G. Tipping and S. R. Holdsworth
T Cells in Crescentic Glomerulonephritis
J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1253 - 1263.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
D. Odobasic, A. R. Kitching, T. J. Semple, and S. R. Holdsworth
Inducible Co-Stimulatory Molecule Ligand Is Protective during the Induction and Effector Phases of Crescentic Glomerulonephritis
J. Am. Soc. Nephrol., April 1, 2006; 17(4): 1044 - 1053.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
J. R. Timoshanko, R. Kitching, T. J. Semple, P. G. Tipping, and S. R. Holdsworth
A Pathogenetic Role for Mast Cells in Experimental Crescentic Glomerulonephritis
J. Am. Soc. Nephrol., January 1, 2006; 17(1): 150 - 159.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
S. E. Wenderfer, B. Ke, T. J. Hollmann, R. A. Wetsel, H. Y. Lan, and M. C. Braun
C5a Receptor Deficiency Attenuates T Cell Function and Renal Disease in MRLlpr Mice
J. Am. Soc. Nephrol., December 1, 2005; 16(12): 3572 - 3582.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
A. R. Kitching, A. L. Turner, G. R.A. Wilson, T. Semple, D. Odobasic, J. R. Timoshanko, K. M. O'Sullivan, P. G. Tipping, K. Takeda, S. Akira, et al.
IL-12p40 and IL-18 in Crescentic Glomerulonephritis: IL-12p40 is the Key Th1-Defining Cytokine Chain, Whereas IL-18 Promotes Local Inflammation and Leukocyte Recruitment
J. Am. Soc. Nephrol., July 1, 2005; 16(7): 2023 - 2033.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
D. Odobasic, A. R. Kitching, T. J. Semple, J. R. Timoshanko, P. G. Tipping, and S. R. Holdsworth
Glomerular Expression of CD80 and CD86 Is Required for Leukocyte Accumulation and Injury in Crescentic Glomerulonephritis
J. Am. Soc. Nephrol., July 1, 2005; 16(7): 2012 - 2022.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
D. Wolf, K. Hochegger, A. M. Wolf, H. F. Rumpold, G. Gastl, H. Tilg, G. Mayer, E. Gunsilius, and A. R. Rosenkranz
CD4+CD25+ Regulatory T Cells Inhibit Experimental Anti-Glomerular Basement Membrane Glomerulonephritis in Mice
J. Am. Soc. Nephrol., May 1, 2005; 16(5): 1360 - 1370.
[Abstract] [Full Text] [PDF]

Home page
 LupusHome page
E J Lewis and M M Schwartz
Pathology of lupus nephritis
Lupus, January 1, 2005; 14(1): 31 - 38.
[Abstract] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
A. R. Kitching, A. L. Turner, G. R.A. Wilson, K. L. Edgtton, P. G. Tipping, and S. R. Holdsworth
Endogenous IL-13 Limits Humoral Responses and Injury in Experimental Glomerulonephritis but Does Not Regulate Th1 Cell-Mediated Crescentic Glomerulonephritis
J. Am. Soc. Nephrol., September 1, 2004; 15(9): 2373 - 2382.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A.-J. Ruth, A. R. Kitching, M. Li, T. J. Semple, J. R. Timoshanko, P. G. Tipping, and S. R. Holdsworth
An IL-12-Independent Role for CD40-CD154 in Mediating Effector Responses: Studies in Cell-Mediated Glomerulonephritis and Dermal Delayed-Type Hypersensitivity
J. Immunol., July 1, 2004; 173(1): 136 - 144.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
A. R. Kitching, A. L. Turner, T. Semple, M. Li, K. L. Edgtton, G. R. Wilson, J. R. Timoshanko, B. G. Hudson, and S. R. Holdsworth
Experimental Autoimmune Anti-Glomerular Basement Membrane Glomerulonephritis: A Protective Role for IFN-{gamma}
J. Am. Soc. Nephrol., July 1, 2004; 15(7): 1764 - 1774.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
G. G. Choudhury
A Linear Signal Transduction Pathway Involving Phosphatidylinositol 3-Kinase, Protein Kinase C{epsilon}, and MAPK in Mesangial Cells Regulates Interferon-{gamma}-induced STAT1{alpha} Transcriptional Activation
J. Biol. Chem., June 25, 2004; 279(26): 27399 - 27409.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
J. R. Timoshanko, A. R. Kitching, Y. Iwakura, S. R. Holdsworth, and P. G. Tipping
Leukocyte-Derived Interleukin-1{beta} Interacts with Renal Interleukin-1 Receptor I to Promote Renal Tumor Necrosis Factor and Glomerular Injury in Murine Crescentic Glomerulonephritis
Am. J. Pathol., June 1, 2004; 164(6): 1967 - 1977.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
J. R. Timoshanko, A. R. Kitching, Y. Iwakura, S. R. Holdsworth, and P. G. Tipping
Contributions of IL-1{beta} and IL-1{alpha} to Crescentic Glomerulonephritis in Mice
J. Am. Soc. Nephrol., April 1, 2004; 15(4): 910 - 918.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
T. Ohse, T. Ota, N. Kieran, C. Godson, K. Yamada, T. Tanaka, T. Fujita, and M. Nangaku
Modulation of Interferon-Induced Genes by Lipoxin Analogue in Anti-Glomerular Basement Membrane Nephritis
J. Am. Soc. Nephrol., April 1, 2004; 15(4): 919 - 927.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
R. M. Tarzi, H. T. Cook, I. Jackson, C. D. Pusey, and G. M. Lord
Leptin-Deficient Mice Are Protected from Accelerated Nephrotoxic Nephritis
Am. J. Pathol., February 1, 2004; 164(2): 385 - 390.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
A.-J. Ruth, A. R. Kitching, T. J. Semple, P. G. Tipping, and S. R. Holdsworth
Intrinsic Renal Cell Expression of CD40 Directs Th1 Effectors Inducing Experimental Crescentic Glomerulonephritis
J. Am. Soc. Nephrol., November 1, 2003; 14(11): 2813 - 2822.
[Abstract] [Full Text] [PDF]

Home page
 Rheumatology (Oxford)Home page
W.-S. Uhm, K. Na, G.-W. Song, S.-S. Jung, T. Lee, M.-H. Park, and D.-H. Yoo
Cytokine balance in kidney tissue from lupus nephritis patients
Rheumatology, August 1, 2003; 42(8): 935 - 938.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
R. M. Tarzi, K. A Davies, J. W. C. Claassens, J. S. Verbeek, M. J. Walport, and H. T. Cook
Both Fc{gamma} Receptor I and Fc{gamma} Receptor III Mediate Disease in Accelerated Nephrotoxic Nephritis
Am. J. Pathol., May 1, 2003; 162(5): 1677 - 1683.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
Y. Ikezumi, R. C. Atkins, and D. J. Nikolic-Paterson
Interferon-{gamma} Augments Acute Macrophage-Mediated Renal Injury Via a Glucocorticoid-Sensitive Mechanism
J. Am. Soc. Nephrol., April 1, 2003; 14(4): 888 - 898.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. R. Timoshanko, S. R. Holdsworth, A. R. Kitching, and P. G. Tipping
IFN-{gamma} Production by Intrinsic Renal Cells and Bone Marrow-Derived Cells Is Required for Full Expression of Crescentic Glomerulonephritis in Mice
J. Immunol., April 15, 2002; 168(8): 4135 - 4141.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
A. R. Kitching, X. Ru Huang, A. L. Turner, P. G. Tipping, A. R. Dunn, and S. R. Holdsworth
The Requirement for Granulocyte-Macrophage Colony-Stimulating Factor and Granulocyte Colony-Stimulating Factor in Leukocyte-Mediated Immune Glomerular Injury
J. Am. Soc. Nephrol., February 1, 2002; 13(2): 350 - 358.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
J. R. TIMOSHANKO, A. R. KITCHING, S. R. HOLDSWORTH, and P. G. TIPPING
Interleukin-12 from Intrinsic Cells Is an Effector of Renal Injury in Crescentic Glomerulonephritis
J. Am. Soc. Nephrol., March 1, 2001; 12(3): 464 - 471.
[Abstract] [Full Text]

Home page
 J. Immunol.Home page
A. R. Kitching, P. G. Tipping, M. Kurimoto, and S. R. Holdsworth
IL-18 Has IL-12-Independent Effects in Delayed-Type Hypersensitivity: Studies in Cell-Mediated Crescentic Glomerulonephritis
J. Immunol., October 15, 2000; 165(8): 4649 - 4657.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
F. Strutz, M. Heeg, T. Kochsiek, G. Siemers, M. Zeisberg, and G. A. Muller
Effects of pentoxifylline, pentifylline and {gamma}-interferon on proliferation, differentiation, and matrix synthesis of human renal fibroblasts
Nephrol. Dial. Transplant., October 1, 2000; 15(10): 1535 - 1546.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
A. F. Drew, H. L. Tucker, H. Liu, D. P. Witte, J. L. Degen, and P. G. Tipping
Crescentic glomerulonephritis is diminished in fibrinogen-deficient mice
Am J Physiol Renal Physiol, December 1, 2001; 281(6): F1157 - F1163.
[Abstract] [Full Text] [PDF]


HOME CURRENT ISSUE ARCHIVES JASN Express ONLINE SUBMISSION AUTHOR INFO
EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673