title: Effects of diesel exhaust particles on antigen-presenting cells and antigen-specific Th immunity in mice.
abstract: Diesel exhaust particles (DEP) exacerbate antigen-related airway inflammation and hyperresponsiveness in mice; however, the mechanisms remain undefined. The present study characterized more precisely which pathways and cellular events of the allergic response are amplified by DEP in view of the maturation/activation/function of antigen-presenting cells (APC) and the antigen-specific Th response. We evaluated the effects of DEP on the phenotype and function of bone marrow-derived dendritic cells (BMDC) in vitro and on the expression pattern of APC-related molecules in the murine lung in the presence or absence of antigen in vivo. Also, we tested the effects of in vivo DEP co-exposure with antigen on the splenic antigen-specific Th response in the context of cytokine production. DEP significantly increased both allogeneic and antigen (ovalbumin: OVA)-specific syngeneic T-cell proliferation in vitro. In addition, an in vivo experiment showed that repetitive pulmonary exposure to DEP plus antigen (OVA) increased the numbers of MHC class II+cells and those expressing CD11c, DEC205 (DC markers), CD80, CD86 (co-stimulatory molecules), F4/80 (a macrophage marker), and CD19 (a B-cell differentiation antigen) in the lung as compared to that of others (vehicle, DEP, or OVA). Furthermore, an ex vivo assay system demonstrated that splenic mononuclear cells primed by DEP plus OVA produced a greater amount of interleukin (IL)-4, IL-5, and IL-13 after in vitro antigen stimulation compared to those primed by the other treatments. In conclusion, enhancement of allergic responses by DEP can be explained via two novel mechanisms, i.e., enhancement effects on APC including DC and on antigen-specific Th response, which culminate in the promotion of local and systemic dysregulated Th immunity.
authors.affiliation: Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba 305-8506, Japan. inoue.kenichirou@nies.go.jp
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Inoue
authors.forename: Eiko
authors.initials: E
authors.lastname: Koike
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Takano
authors.forename: Rie
authors.initials: R
authors.lastname: Yanagisawa
authors.forename: Takamichi
authors.initials: T
authors.lastname: Ichinose
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D000941:Antigens / Q000276:immunology; D001835:Body Weight / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007109:Immunity / Q000187:drug effects*; D007136:Immunoglobulins / Q000276:immunology; D008297:Male; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D052638:Particulate Matter / Q000494:pharmacology*; D011014:Pneumonia / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D001335:Vehicle Emissions
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007136:Immunoglobulins; D052638:Particulate Matter; D001335:Vehicle Emissions; D010047:Ovalbumin