Ability of Trichloroethylene Metabolite to Promote Immune Pathology is Strain-Specific

Abstract

Chronic low-level exposure to the environmental pollutant trichloroethylene has been shown to promote autoimmune disease in association with CD4+ T-lymphocyte activation in lupus-prone MRL+/+ mice. One of the primary metabolites of trichloroethylene, trichloroacetaldehyde hydrate (TCAH), was similarly shown to increase the percentage of IFNγ-producing CD4+ T-lymphocytes when added to the drinking water of MRL+/+ mice. In addition, TCAH-treated MRL+/+ mice developed skin inflammation and alopecia. In the present study TCAH was tested for its ability to accelerate the development of alopecia in C3H/HeJ mice which tend to develop the disorder spontaneously late in life. In contrast to MRL+/+ mice, C3H/HeJ mice treated with TCAH did not develop alopecia at an increased rate. In addition, TCAH did not promote the expansion of activated IFNγ-producing CD4+ T-lymphocytes in C3H/HeJ mice. CD4+ T-lymphocytes from TCAH-treated C3H/HeJ mice, unlike their MRL+/+ counterparts, did not become resistant to activation-induced apoptosis following in vivo exposure to TCAH. Taken together, it appears that the ability of TCAH to promote immune-mediated pathology is strain-specific and may require an autoimmune-prone genetic background.