J. Exp. Med., Volume 188, Number 3, August 3, 1998 597-602

Major Histocompatibility Complex Class II Expression by Intrinsic Renal Cells Is Required for Crescentic Glomerulonephritis

By Shuo Li,^* Christian Kurts, Frank Köntgen, Stephen R. Holdsworth,^* and Peter G. Tipping^*

From the ^* Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, 3168, Victoria, Australia; and the  Immunology Division, Walter and Eliza Hall Institute, Parkville, 3050, Victoria, Australia

The requirement for major histocompatibility complex class II (MHC II) to initiate immune renal injury was studied in a murine model of CD4⁺ T cell-dependent crescentic glomerulonephritis (GN). C57BL/6 (MHC II^+/+) mice developed crescentic GN with glomerular CD4⁺ T cell infiltration and renal injury, in response to a nephritogenic antigen (sheep globulin) planted on their glomerular basement membrane. MHC II-deficient C57BL/6 mice (MHC II^/) did not develop crescentic GN, CD4⁺ T cell infiltration, or injury, indicating that this form of immune glomerular injury is MHC II dependent. The requirement for MHC II expression by intrinsic renal cells was studied in chimeric mice, which expressed MHC II on bone marrow-derived cells and in the thymus, but not in the kidneys. These chimeric mice had normal T and B cell populations and MHC II expression in their spleens and lymph nodes and developed an immune response to systemically and cutaneously administered sheep globulin. However, they did not develop crescentic GN, CD4⁺ T cell infiltration, or renal injury in response to the sheep globulin planted in their glomeruli. These studies demonstrate that interaction of CD4⁺ T cells with intrinsic renal cells expressing MHC II is required for development of cell-mediated immune renal injury.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Xie, C., Rahman, Z. S. M., Xie, S., Zhu, J., Du, Y., Qin, X., Zhou, H., Zhou, X. J., Mohan, C. (2008). Strain distribution pattern of immune nephritis--a follow-up study. Int Immunol 20: 719-728 [Abstract] [Full Text]  
• Matte-Martone, C., Liu, J., Jain, D., McNiff, J., Shlomchik, W. D. (2008). CD8+ but not CD4+ T cells require cognate interactions with target tissues to mediate GVHD across only minor H antigens, whereas both CD4+ and CD8+ T cells require direct leukemic contact to mediate GVL. Blood 111: 3884-3892 [Abstract] [Full Text]  
• Scholz, J., Lukacs-Kornek, V., Engel, D. R., Specht, S., Kiss, E., Eitner, F., Floege, J., Groene, H.-J., Kurts, C. (2008). Renal Dendritic Cells Stimulate IL-10 Production and Attenuate Nephrotoxic Nephritis. J. Am. Soc. Nephrol. 19: 527-537 [Abstract] [Full Text]  
• Tipping, P. G., Holdsworth, S. R. (2006). T Cells in Crescentic Glomerulonephritis. J. Am. Soc. Nephrol. 17: 1253-1263 [Abstract] [Full Text]  
• Timoshanko, J. R., Kitching, A. R., Semple, T. J., Holdsworth, S. R., Tipping, P. G. (2005). Granulocyte Macrophage Colony-Stimulating Factor Expression by Both Renal Parenchymal and Immune Cells Mediates Murine Crescentic Glomerulonephritis. J. Am. Soc. Nephrol. 16: 2646-2656 [Abstract] [Full Text]  
• Wolf, D., Hochegger, K., Wolf, A. M., Rumpold, H. F., Gastl, G., Tilg, H., Mayer, G., Gunsilius, E., Rosenkranz, A. R. (2005). CD4+CD25+ Regulatory T Cells Inhibit Experimental Anti-Glomerular Basement Membrane Glomerulonephritis in Mice. J. Am. Soc. Nephrol. 16: 1360-1370 [Abstract] [Full Text]  
• Lang, A., Benke, D., Eitner, F., Engel, D., Ehrlich, S., Breloer, M., Hamilton-Williams, E., Specht, S., Hoerauf, A., Floege, J., von Bonin, A., Kurts, C. (2005). Heat Shock Protein 60 Is Released in Immune-Mediated Glomerulonephritis and Aggravates Disease: In Vivo Evidence for an Immunologic Danger Signal. J. Am. Soc. Nephrol. 16: 383-391 [Abstract] [Full Text]  
• Ruth, A.-J., Kitching, A. R., Li, M., Semple, T. J., Timoshanko, J. R., Tipping, P. G., Holdsworth, S. R. (2004). An IL-12-Independent Role for CD40-CD154 in Mediating Effector Responses: Studies in Cell-Mediated Glomerulonephritis and Dermal Delayed-Type Hypersensitivity. J. Immunol. 173: 136-144 [Abstract] [Full Text]  
• Timoshanko, J. R., Kitching, A. R., Iwakura, Y., Holdsworth, S. R., Tipping, P. G. (2004). 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. 164: 1967-1977 [Abstract] [Full Text]  
• Kruger, T., Benke, D., Eitner, F., Lang, A., Wirtz, M., Hamilton-Williams, E. E., Engel, D., Giese, B., Muller-Newen, G., Floege, J., Kurts, C. (2004). Identification and Functional Characterization of Dendritic Cells in the Healthy Murine Kidney and in Experimental Glomerulonephritis. J. Am. Soc. Nephrol. 15: 613-621 [Abstract] [Full Text]  
• Cairns, L. S., Phelps, R. G., Bowie, L., Hall, A. M., Saweirs, W. W.M., Rees, A. J., Barker, R. N. (2003). The Fine Specificity and Cytokine Profile of T-Helper Cells Responsive to the {alpha}3 Chain of Type IV Collagen in Goodpasture's Disease. J. Am. Soc. Nephrol. 14: 2801-2812 [Abstract] [Full Text]  
• Ruth, A.-J., Kitching, A. R., Semple, T. J., Tipping, P. G., Holdsworth, S. R. (2003). Intrinsic Renal Cell Expression of CD40 Directs Th1 Effectors Inducing Experimental Crescentic Glomerulonephritis. J. Am. Soc. Nephrol. 14: 2813-2822 [Abstract] [Full Text]  
• Suzuki, Y., Gomez-Guerrero, C., Shirato, I., Lopez-Franco, O., Hernandez-Vargas, P., Sanjuan, G., Ruiz-Ortega, M., Sugaya, T., Okumura, K., Tomino, Y., Ra, C., Egido, J. (2002). Susceptibility to T Cell-Mediated Injury in Immune Complex Disease Is Linked to Local Activation of Renin-Angiotensin System: The Role of NF-AT Pathway. J. Immunol. 169: 4136-4146 [Abstract] [Full Text]  
• Waldburger, J.-M., Suter, T., Fontana, A., Acha-Orbea, H., Reith, W. (2001). Selective Abrogation of Major Histocompatibility Complex Class II Expression on Extrahematopoietic Cells in Mice Lacking Promoter IV of the Class II Transactivator Gene. JEM 194: 393-406 [Abstract] [Full Text]  
• TIMOSHANKO, J. R., KITCHING, A. R., HOLDSWORTH, S. R., TIPPING, P. G. (2001). Interleukin-12 from Intrinsic Cells Is an Effector of Renal Injury in Crescentic Glomerulonephritis. J. Am. Soc. Nephrol. 12: 464-471 [Abstract] [Full Text]  
• Lou, Y.-H., Park, K.-K., Agersborg, S., Alard, P., Tung, K. S. K. (2000). Retargeting T Cell-Mediated Inflammation: A New Perspective on Autoantibody Action. J. Immunol. 164: 5251-5257 [Abstract] [Full Text]  
• Cunningham, M. A., Rondeau, E., Chen, X., Coughlin, S. R., Holdsworth, S. R., Tipping, P. G. (2000). Protease-activated Receptor 1 Mediates Thrombin-dependent, Cell-mediated Renal Inflammation in Crescentic Glomerulonephritis. JEM 191: 455-462 [Abstract] [Full Text]  
• Jenks, S. A., Miller, J. (2000). Inhibition of IL-4 Responses After T Cell Priming in the Context of LFA-1 Costimulation Is Not Reversed by Restimulation in the Presence of CD28 Costimulation. J. Immunol. 164: 72-78 [Abstract] [Full Text]  
• KITCHING, A. R., HOLDSWORTH, S. R., TIPPING, P. G. (1999). IFN-{gamma} Mediates Crescent Formation and Cell-Mediated Immune Injury in Murine Glomerulonephritis. J. Am. Soc. Nephrol. 10: 752-759 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS