International Immunology, Vol. 11, No. 6, 925-931,
June 1999
© 1999 Japanese Society for Immunology
Therapeutic effect of an anti-Fas ligand mAb on lethal graft-versus-host disease
1 Department of Molecular Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan
2 Department of Orthopaedic Surgery, Osaka University Medical School, Osaka 565-0871, Japan
3 Biosciences Research Laboratory, Mochida Pharmaceutical Co., Ltd, Tokyo 115-0043, Japan
4 Department of Genetics, Osaka University Medical School, Osaka 565-0871, Japan
5 Center for the Development of Molecular Target Drugs, Cancer Research Institute, Kanazawa University, Kanazawa 920-0934, Japan
Correspondence to: T. Suda, Center for the Development of Molecular Target Drugs, Cancer Research Institute, Kanazawa University, 13-1 Takaramachi, Kanazawa 920-0934, Japan
Several anti-Fas ligand (FasL) inhibitory mAb (FLIM) were raised and characterized in this study. One, FLIM58, showed more potent neutralizing activity than Fas-Fc, the previously established artificial neutralizing agent for FasL. Several murine models of acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation have been used to show that both FasL and perforin, the major effector molecules of cytotoxic T lymphocytes, are involved in this disease. In our GVHD model, FasL rather than perforin was associated with lethality. Administration of FLIM58 or Fas-Fc reduced the weight loss and mortality caused by GVHD, although other signs of GVHD, such as skin lesions, lymphoid hypoplasia and mononuclear cell infiltration in the liver, did not improve significantly. FLIM58 was more effective than Fas-Fc in reducing mortality. Our results demonstrated that neutralizing agents for FasL are therapeutic for lethal GVHD.
Keywords: apoptosis, bone marrow transfer, cytotoxic T lymphocyte, disease model
Transmitting editor: D. Kitamura
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. A. Rotolo, B. Stancevic, S. X. Lu, J. Zhang, D. Suh, C. G. King, L. W. Kappel, G. F. Murphy, C. Liu, Z. Fuks, et al. Cytolytic T cells induce ceramide-rich platforms in target cell membranes to initiate graft-versus-host disease Blood, October 22, 2009; 114(17): 3693 - 3706. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kidoya, M. Umemura, T. Kawabe, G. Matsuzaki, A. Yahagi, R. Imamura, and T. Suda Fas Ligand Induces Cell-Autonomous IL-23 Production in Dendritic Cells, a Mechanism for Fas Ligand-Induced IL-17 Production J. Immunol., December 15, 2005; 175(12): 8024 - 8031. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Iwasaki Recent Advances in the Treatment of Graft-Versus-Host Disease Clin. Med. Res., November 1, 2004; 2(4): 243 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Umemura, T. Kawabe, K. Shudo, H. Kidoya, M. Fukui, M. Asano, Y. Iwakura, G. Matsuzaki, R. Imamura, and T. Suda Involvement of IL-17 in Fas ligand-induced inflammation Int. Immunol., August 1, 2004; 16(8): 1099 - 1108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fukui, R. Imamura, M. Umemura, T. Kawabe, and T. Suda Pathogen-Associated Molecular Patterns Sensitize Macrophages to Fas Ligand-Induced Apoptosis and IL-1{beta} Release J. Immunol., August 15, 2003; 171(4): 1868 - 1874. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Nakamoto, S. Kaneko, H. Fan, T. Momoi, H. Tsutsui, K. Nakanishi, K. Kobayashi, and T. Suda Prevention of Hepatocellular Carcinoma Development Associated with Chronic Hepatitis by Anti-Fas Ligand Antibody Therapy J. Exp. Med., October 21, 2002; 196(8): 1105 - 1111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Merger, J L Viney, R Borojevic, D Steele-Norwood, P Zhou, D A Clark, R Riddell, R Maric, E R Podack, and K Croitoru Defining the roles of perforin, Fas/FasL, and tumour necrosis factor {alpha} in T cell induced mucosal damage in the mouse intestine Gut, August 1, 2002; 51(2): 155 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Saegusa, N. Ishimaru, K. Yanagi, K. Mishima, R. Arakaki, T. Suda, I. Saito, and Y. Hayashi Prevention and Induction of Autoimmune Exocrinopathy Is Dependent on Pathogenic Autoantigen Cleavage in Murine Sjogren's Syndrome J. Immunol., July 15, 2002; 169(2): 1050 - 1057. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.B. Sugerman, N.W. Savage, L.J. Walsh, Z.Z. Zhao, X.J. Zhou, A. Khan, G.J. Seymour, and M. Bigby THE PATHOGENESIS OF ORAL LICHEN PLANUS Critical Reviews in Oral Biology & Medicine, July 1, 2002; 13(4): 350 - 365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Ishimaru, K. Yanagi, K. Ogawa, T. Suda, I. Saito, and Y. Hayashi Possible Role of Organ-Specific Autoantigen for Fas Ligand-Mediated Activation-Induced Cell Death in Murine Sjogren's Syndrome J. Immunol., November 15, 2001; 167(10): 6031 - 6037. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Takahashi, H. Kosaka, K. Oritani, W. R. Heath, J. Ishikawa, Y. Okajima, M. Ogawa, S.-i. Kawamoto, M. Yamada, H. Azukizawa, et al. A New IFN-Like Cytokine, Limitin Modulates the Immune Response Without Influencing Thymocyte Development J. Immunol., September 15, 2001; 167(6): 3156 - 3163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Matsushima, M. Nakashima, K. Oshima, Y. Abe, J. Nishimura, H. Nawata, T. Watanabe, and K. Muta Receptor binding cancer antigen expressed on SiSo cells, a novel regulator of apoptosis of erythroid progenitor cells Blood, July 15, 2001; 98(2): 313 - 321. [Abstract] [Full Text] [PDF]
|
|