Trichloroethylene activates CD4+ T cells: potential role in an autoimmune response.
Trichloroethylene is an industrial solvent and has become a major environmental contaminant. Autoimmune-prone MRL +/+ mice were treated for up to 22 weeks with trichloroethylene in the drinking water (0, 2.5, and 5.0 mg/mL) in order to study the immunoregulatory effects of this environmental toxicant. After only 4 weeks of treatment, trichloroethylene was shown to promote the expansion of CD4+ T cells that expressed a memory/activation phenotype (i.e., CD44hi CD45RBlo) and secreted high levels of IFN-gamma, but not IL-4. In addition, trichloroethylene treatment accelerated the development of an autoimmune response in the MRL +/+ mice as evidenced by an earlier appearance of antinuclear antibodies and increased levels of total IgG2a. MRL +/+ mice treated with trichloroethylene for 22 weeks also contained antibodies specific for trichloroethylene adducts, suggesting the activation of trichloroethylene-specific T cells. The results suggest that trichloroethylene can stimulate antigen nonspecific as well as specific T cells that are capable of promoting autoimmunity in genetically predisposed individuals.
Gilbert
K M
KM
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
Griffin
J M
JM
Pumford
N R
NR
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood / Q000187:drug effects; D015551:Autoimmunity / Q000187:drug effects* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D004195:Disease Models, Animal; D018960:Hyaluronan Receptors / Q000187:drug effects / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood / Q000187:drug effects*; D017493:Leukocyte Common Antigens / Q000187:drug effects / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D019463:Mice, Inbred MRL lpr; D012997:Solvents / Q000378:metabolism / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D014241:Trichloroethylene / Q000097:blood / Q000494:pharmacology*
D000974:Antibodies, Antinuclear; D015415:Biomarkers; D018960:Hyaluronan Receptors; D007074:Immunoglobulin G; D012997:Solvents; D014241:Trichloroethylene; D017493:Leukocyte Common Antigens