title: Trichloroethylene enhances TCR-CD3-induced proliferation of CD8(+) rather than CD4(+) T cells.
abstract: Trichloroethylene (TCE) is suspected as a potent immunomodulator that accelerates the development of allergic diseases. We previously reported that TCE promotes ovalbumin (OVA)-induced active cutaneous anaphylaxis, including enhancing antigen-specific serum IgE levels and splenic lymphocyte proliferation. However, the target cells and molecular mechanism through which TCE modulates antigen-specific immune responses remain unclear. To identify a potential underlying mechanism, we investigated whether TCE modulates T cell receptor (TCR)-induced T cell activation and proliferation in vitro. TCE enhanced T cell proliferation primed by anti-CD3 antibody, but not concanavalin A, in a dose-dependent fashion. In addition, TCE enhanced anti-CD3-primed proliferation of CD8(+) rather than CD4(+) T cells. Consistent with this result, TCE markedly enhanced the Lck phosphorylation mediated by anti-CD3 antibody in CD8(+) but not CD4(+) T cells. Furthermore, we analyzed the effect of TCE exposure via drinking water for 2 weeks on splenocyte populations in non-immunized and OVA-immunized mice. In OVA-immunized mice, TCE (3 mg/l) significantly expanded CD3(+), CD8(+) and CD4(+) cell populations, however the effect at the lower concentration was significant only in the CD8(+) populations, whereas TCE had no effect on these cells population in non-immunized mice. These findings suggest that TCE enhances TCR-CD3-induced proliferation of CD8(+) rather than CD4(+) cells and disrupts various activities of peripheral T cells.
authors.affiliation: Laboratory of Hygienic Chemistry and Molecular Toxicology, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Kobayashi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nakanishi
authors.forename: Hisamitsu
authors.initials: H
authors.lastname: Nagase
mesh_terms: D000485:Allergens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D007155:Immunologic Factors / Q000633:toxicity*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D012997:Solvents / Q000633:toxicity*; D014241:Trichloroethylene / Q000633:toxicity*; D014611:Vaccination
chemical_list: D000485:Allergens; D017252:CD3 Complex; D007155:Immunologic Factors; D011948:Receptors, Antigen, T-Cell; D012997:Solvents; D014241:Trichloroethylene; D010047:Ovalbumin; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)