Effects of anti-CD70 mAb on Theiler's murine encephalomyelitis virus-induced demyelinating disease.
Ligation of CD27, a member of the tumor necrosis factor (TNF) receptor family, by its ligand CD70 is thought to be important in T cell activation, expansion and survival, B cell activation, and NK cell activation. We examined the role of CD70 in Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) mice. Blocking of CD70 in effector phase by anti-CD70 monoclonal antibody (mAb) suppressed the development of TMEV-IDD. The number of IFN-gamma- or TNF-alpha-producing cells in the spleen and mRNA levels of IFN-gamma and TNF-alpha in spinal cord were decreased in mice treated with anti-CD70 mAb at the effector phase. In contrast, treatment with anti-CD70 mAb in induction phase failed to reduce these responses, compared to nonspecific IgG-treated control mice. These data suggest that CD70 is critically involved in the pathogenesis of TMEV-IDD and that antibodies against CD70 could be a novel therapeutic approach in the clinical treatment of demyelinating diseases such as human multiple sclerosis.
Yanagisawa
Satoshi
S
Department of Biomedical Laboratory Sciences, Shinshu University, Matsumoto, Nagano 390-8621, Japan.
Takeichi
Naoya
N
Kaneyama
Tomoki
T
Yagita
Hideo
H
Taniguchi
Syun'ichiro
S
Kim
Byung S
BS
Koh
Chang-Sung
CS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D053282:CD27 Ligand / Q000276:immunology* / Q000502:physiology; D018188:Cardiovirus Infections / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D003711:Demyelinating Diseases / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D005260:Female; D007155:Immunologic Factors / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D017945:Theilovirus; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D053282:CD27 Ligand; D016207:Cytokines; D007155:Immunologic Factors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma