Trichloroethylene Alters Central and Peripheral Immune Function in Autoimmune-Prone MRL+/+ Mice Following Continuous Developmental and Early Life Exposure

Abstract

Trichloroethylene (TCE) is a widespread environmental toxicant known to promote CD4+ T-lymphocyte activation, IFNγ production, and autoimmunity in adult MRL+/+ mice. Because developing tissues may be more sensitive to toxicant exposure, it was hypothesized that continuous TCE exposure beginning at conception might induce even more pronounced CD4+ T-lymphocyte effects and exacerbate the development of autoimmunity in MRL+/+ mice. In the current study, MRL+/+ mice were exposed to occupationally-relevant doses of TCE from conception until adulthood (i.e., 7–8 wk-of-age). The CD4+ T-lymphocyte effects in the thymus and periphery were evaluated, as well as serum antibody levels. TCE exposure altered the number of thymocyte subsets, and reduced the capacity of the most immature CD4−/CD8− thymocytes to undergo apoptosis in vitro. In the periphery, T-lymphocyte IFNγ production was monitored in the blood prior to sacrifice by intracellular cytokine staining and flow cytometry. TCE induced a dose-dependent increase in T-lymphocyte IFNγ as early as 4–5-week-of-age. However, these effects were transient, and not observed in splenic T-lymphocytes in 7–8-week-old mice. In contrast, the serum levels of anti-histone autoantibodies and total IgG2a were significantly elevated in the TCE-exposed offspring. The data illustrated that occupationally-relevant doses of TCE administered throughout development until adulthood affected central and peripheral immune function in association with early signs of autoimmunity. Future studies will address the possibility that early-life exposure to TCE may alter some aspect of self tolerance in the thymus, leading to autoimmune disease later in life.