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Blood, Vol. 95 No. 7 (April 1), 2000:
pp. 2434-2439
Blockade of CD134 (OX40)-CD134L interaction ameliorates lethal
acute graft-versus-host disease in a murine model of allogeneic
bone marrow transplantation
Nobuhiro Tsukada,
Hisaya Akiba,
Tetsuji Kobata,
Yoshifusa Aizawa,
Hideo Yagita, and
Ko Okumura
From the Department of Immunology, Juntendo University School of
Medicine, Tokyo, Japan; 1st Department of Internal Medicine, Niigata
University School of Medicine, Niigata, Japan; CREST (Core Research for
Evolutional Science and Technology) of Japan Science and Technology
Corporation (JST), Tokyo, Japan; and the Division of Immunology,
Institute for Medical Science, Dokkyo University School of Medicine,
Tochigi, Japan.
Expression of CD134 (OX40) on activated CD4+ T cells
has been observed in acute graft-versus-host disease (GVHD) after human and rat allogeneic bone marrow transplantation (BMT). We investigated the role of interaction between CD134 and CD134 ligand (CD134L) in a
murine model of acute GVHD by using a newly established monoclonal antibody (mAb) against murine CD134L. Acute GVHD was induced by transfer of bone marrow cells and spleen cells into lethally irradiated recipients in a parent (C57BL/6) to first filial generation (C57BL/6 crossed with DBA/2) BMT. Administration of anti-CD134L mAb
significantly reduced the lethality of acute GVHD and other
manifestations of the disease, such as loss of body weight, hunched
posture, diarrhea, and patchy alopecia. The survival rate 80 days after
BMT in mice treated with the mAb was about 70%, whereas all mice
treated with control antibodies died within 43 days. Histologic
examinations revealed that inflammatory changes in target organs such
as the liver, gut, and skin were also ameliorated in mice treated with the mAb compared with control mice. An in vitro assay of T-cell proliferation showed a marked hyporesponsiveness to host alloantigen in
samples from mice treated with anti-CD134L mAb. In addition, low levels
of interferon  and transiently elevated levels of interleukin 4 and
IgE in serum samples were found in mice treated with anti-CD134L mAb.
These results suggest that CD134-CD134L interactions have an important
role in the pathogenesis of acute GVHD.
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