title: Blockade of CD70-CD27 interaction inhibits induction of allergic lung inflammation in mice.
abstract: The interaction between the TNF receptor family member CD27 and its ligand CD70 provides a costimulatory signal for T-cell activation. In this study, we investigated the effects of neutralizing anti-CD70 monoclonal antibody (mAb) in a murine model of allergic lung inflammation to determine whether CD27 contributes to the development of pathogenic Th2 cells and pulmonary inflammation. BALB/c mice were immunized by an injection of ovalbumin (OVA) with alum adjuvant and challenged with aerosolized OVA in PBS. Some groups of mice were treated with anti-CD70 mAb or control rat IgG during the induction or effector phase. The administration of anti-CD70 mAb during the induction phase, but not the effector phase, reduced eosinophil infiltration in lung tissue compared with control IgG-treated mice. Treatment with anti-CD70 mAb also resulted in the decreased production of Th2 cytokines (IL-4, IL-5, and IL-13) in the bronchoalveolar lavage fluid and draining lymph node cell cultures. We further revealed that antigen-specific CD4 T cells were separated into CD27(+) and CD27(-) populations in the lymph nodes of OVA-immunized DO11.10/Rag-2(-/-) mice. The CD27(+) CD4 T cells produced a high concentration of IFN-γ, representing Th1 cells. In contrast, CD27(-) CD4 T cells produced high concentrations of IL-4, IL-5, and IL-13, representing Th2 cells. Moreover, the population of CD27(-) Th2 cells was significantly reduced by the anti-CD70 mAb treatment. These results indicate an important role for CD27 in the development of pathogenic Th2 cells in a murine model of allergic lung inflammation.
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Makino
authors.forename: Jun
authors.initials: J
authors.lastname: Ito
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Abe
authors.forename: Norihiro
authors.initials: N
authors.lastname: Harada
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Kamachi
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takahashi
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Hisaya
authors.initials: H
authors.lastname: Akiba
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D053282:CD27 Ligand / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000276:immunology / Q000628:therapy*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D053282:CD27 Ligand; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7