title: Induction of the imbalance of helper T-cell functions in mice exposed to diesel exhaust.
abstract: Administration of diesel exhaust particles (DEP) increases antigen-specific IgE production and IgE-secreting cells, and induces Th2-type cytokine profiles in the airway in mice and humans. To determine the early effects of diesel exhaust (DE) inhalation on the cytokine production profile, BALB/c mice were exposed to 0 (controls) and 1.0 mg/m3 DE inhalation for 4 weeks. Intraperitoneal sensitization with ovalbumin (OVA) was conducted immediately before DE inhalation. Mice were treated with anti-CD4 or anti-CD8 mAb 1 day before and after the sensitization. On day 21, these mice were boosted with OVA and blood; bronchoalveolar lavage (BAL) fluid, and spleens were collected on day 28. In BAL fluid, both TNFalpha and IL-10 production in DE-exposed and control mice remained basically the same. IL-6 production in the anti-CD4 treatment group of DE-exposed mice, however, significantly increased compared with that of the controls. In vitro antigen-stimulated interleukin-4 (IL-4) and -10 (IL-10) production in spleen cells of exposed mice were not affected by low-dose DE inhalation. In vitro interferon (IFN)-gamma production in the anti-CD4 treated group of exposed mice decreased markedly. Although anti-OVA IgE production in the plasma of sham-treated mice exposed to DE was the same level as for controls, anti-CD4 mAb treatment in DE-exposed mice significantly reduced IgE production compared to controls. In anti-OVA IgG1 production, anti-CD4 or anti-CD8 mAb treatment in DE-exposed groups also significantly reduced. Anti-OVA IgG2a production was reduced by treatment with anti-CD4 mAb, but increased by anti-CD8 mAb treatment in DE-exposed mice. Low dose DE inhalation is thus shown to adversely affect the cytokine and antibody production in mice by altering CD4+ and CD8+ T-cell functions.
authors.affiliation: Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Fujimaki
authors.forename: H
authors.initials: H
authors.lastname: Ushio
authors.forename: K
authors.initials: K
authors.lastname: Nohara
authors.forename: N
authors.initials: N
authors.lastname: Ui
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology*; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens; D016207:Cytokines; D007074:Immunoglobulin G; D001335:Vehicle Emissions; D016753:Interleukin-10; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin