Activation and attenuation of apoptosis of CD4+ T cells following in vivo exposure to two common environmental toxicants, trichloroacetaldehyde hydrate and trichloroacetic acid.
Exposure to occupationally relevant concentrations of the environmental pollutant, trichloroethylene (TCE), in the drinking water of autoimmune-prone MRL+/+ mice has been shown to promote the generation of lupus and autoimmune hepatitis in association with the activation of Interferon-gamma (IFN-gamma)-producing CD4+ T cells. Since blocking TCE metabolism suppressed the TCE-induced alteration in immune function, the present study was initiated to determine whether the major metabolites of TCE, trichloroacetaldehyde hydrate (TCAH) and trichloroacetic acid (TCA) could also mediate these immunoregulatory affects in vivo. TCAH and TCA were administered to the drinking water of MRL+/+ mice for 4 weeks. CD4+ T cells from TCAH and TCA-treated MRL+/+ mice, unlike CD4+ T cells from control mice, demonstrated functional and phenotypic signs of activation, as evidenced by increased IFN-gamma production in association with the increased percentage of CD62L(lo) CD4+ T cells. Interestingly, it was also found that the CD4+ T cells from the TCAH and TCA-treated mice showed a decreased susceptibility to the activation-induced cell death (AICD) form of apoptosis following re-stimulation in vitro. By demonstrating that TCAH and TCA can activate CD4+ T cells and inhibit their apoptosis following in vivo exposure represents a mechanism by which environmental toxicants may induce or accelerate the development of autoimmune disease.
Blossom
Sarah J
SJ
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, 1120 Marshall Street, Little Rock, AR 72205, USA. blossomsarah@uams.edu
Pumford
Neil R
NR
Gilbert
Kathleen M
KM
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D002697:Chloral Hydrate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D010641:Phenotype; D014238:Trichloroacetic Acid / Q000494:pharmacology*
D017304:Annexin A5; D001323:Autoantibodies; D019041:L-Selectin; D002697:Chloral Hydrate; D014238:Trichloroacetic Acid; D007371:Interferon-gamma; C021100:trichloroacetaldehyde