Trichloroethylene accelerates an autoimmune response by Th-1 T cell activation in MRL+/+mice

Trichloroethylene (1,1,2-trichloroethene) is a major environmental contamin ant. There is increasing evidence relating exposure to trichloroethylene wi th autoimmunity. To investigate potential mechanisms, we treated the autoim mune-prone MRL + / + mice with trichloroethylene in the drinking water at 0 , 2.5 or 5.0 mg/ml and sacrificed them at 4, 8 and 22 weeks. As early as 4 weeks of treatment, Western blot analysis showed a dose-dependent increase in the level of trichloroethylene-modified proteins, indicating that a reac tive metabolite of trichloroethylene was formed. Significant increases in a ntinuclear antibodies (ANA) and total serum immunoglobulins were found foll owing 4-8 weeks of trichloroethylene treatment, indicating that trichloroet hylene was accelerating an autoimmune response. Investigation into possible mechanisms of this autoimmune response revealed that trichloroethylene tre atment dramatically increased the expression of the activation marker CD44 on splenic CD44(+) T cells at 4 weeks, in addition, splenic T cells from mi ce treated for 4 weeks with trichloroethylene secreted more IFN-gamma and l ess IL-4 than control T cells, consistent of a T-helper type 1 (Th-1) type immune or inflammatory response. A specific immune response directed agains t dichloroacetylated proteins was found at 22 weeks of trichloroethylene tr eatment. Taken collectively, the results suggest that trichloroethylene tre atment accelerated an autoimmune response characteristic of MRL + / + mice in association with nonspecific activation of Th cells. In addition, long-t erm treatment with trichloroethylene led to the initiation of a trichloroet hylene-specific immune response. (C) 2000 Published by Elsevier Science B.V . All rights reserved.