title: Environmental contaminant trichloroethylene promotes autoimmune disease and inhibits T-cell apoptosis in MRL(+/+) mice.
abstract: The ability of environmental contaminant trichloroethylene to alter immune function and promote autoimmunity was tested in female MRL(+/+) mice. MRL(+/+) mice exposed to occupationally relevant doses of trichloroethylene in their drinking water for 32 weeks developed autoantibodies and pathological evidence of autoimmune hepatitis. The ability of trichloroethylene (TCE) to promote autoimmunity was associated with the expansion of activated (CD44(hi) CD62L(lo)) CD4(+) T-lymphocytes that produced increased levels of the pro-inflammatory cytokine interferon (IFN)-gamma. Activated T-lymphocytes can accumulate if activation-induced apoptosis is suppressed. Consequently, the effect of TCE on apoptosis in CD4(+) T-lymphocytes was investigated. These experiments were conducted with TCE and one of the major oxidative metabolites of trichloroethylene, namely trichloroacetaldehyde hydrate (TCAH). CD4(+) T-lymphocytes isolated from MRL(+/+) mice exposed to TCE or TCAH in their drinking water for 4 weeks were resistant to activation-induced apoptosis in vitro. The TCE-or TCAH-induced decrease in activation-induced apoptosis was associated with decreased expression of FasL, one of the cell surface molecules that mediate apoptosis. These results suggest that exposure to the common water contaminant TCE or its metabolite TCAH inhibits activation-induced apoptosis in CD4+ T-lymphocytes, thereby promoting autoimmune disease by suppressing the process that would otherwise delete activated self-reactive T-lymphocytes.
authors.affiliation: Department of Microbiology and Immunology, University of Arkansas for Medical Sciences/Arkansas Children's Hospital Research Institute, Little Rock, Arkansas 72202, USA. gilbertkathleenm@uams.edu
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Gilbert
authors.forename: Neil R
authors.initials: NR
authors.lastname: Pumford
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Blossom