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Differential Effects of Anti-Fas Ligand and Anti-Tumor Necrosis
Factor  Antibodies on Acute Graft-Versus-Host Disease
Pathologies
Koichi Hattori,
Takao Hirano,
Hiroaki Miyajima,
Norifumi Yamakawa,
Masatoshi Tateno,
Kazuo Oshimi,
Nobuhiko Kayagaki,
Hideo Yagita, and
Ko Okumura
From the Division of Hematology, Department of Internal Medicine, and
the Division of Pathobiology, Department of Immunology, Juntendo
University School of Medicine, Tokyo, Japan; and the Department of
Pathology, Sapporo City General Hospital, Sapporo, Japan; and CREST
(Core Research for Evolutional Science and Technology) of Japan Science
and Technology Corporation (JST), Tokyo, Japan.
Both tumor necrosis factor  (TNF) and Fas ligand (FasL) have
been implicated in the pathogenesis of graft-versus-host disease (GVHD). In this study, we examined the ameliorating effects of neutralizing anti-FasL and/or anti-TNF monoclonal antibody
(MoAb) in a lethal acute GVHD model in mice. Whereas the treatment with either anti-FasL or anti-TNF MoAb alone significantly delayed the
mortality and improved the body weight, a complete protection was
achieved by the administration of both MoAbs. Pathological examination
indicated differential effects of anti-FasL or anti-TNF MoAb on
GVHD-associated pathologies. Hepatic lesion was improved by anti-FasL
but not anti-TNF MoAb. In contrast, intestinal lesion was improved
by anti-TNF but not anti-FasL MoAb. Cutaneous and splenic lesions
were improved by either MoAb. The combination of both MoAbs improved
all these lesions. These results indicate that FasL and TNF
differentially contribute to the GVHD pathologies and a complete
protection from mortality can be achieved by neutralization of both
FasL and TNF.
Blood, Vol. 91 No. 11 (June 1), 1998:
pp. 4051-4055
© 1998 by The American Society of Hematology.
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