Developmental exposure to trichloroethylene promotes CD4+ T cell differentiation and hyperactivity in association with oxidative stress and neurobehavioral deficits in MRL+/+ mice.
The non adult immune system is particularly sensitive to perinatal and early life exposures to environmental toxicants. The common environmental toxicant, trichloroethylene (TCE), was shown to increase CD4+ T cell production of the proinflammatory cytokine IFN-gamma following a period of prenatal and lifetime exposure in autoimmune-prone MRL+/+ mice. In the current study, MRL+/+ mice were used to further examine the impact of TCE on the immune system in the thymus and periphery. Since there is considerable cross-talk between the immune system and the brain during development, the potential relationship between TCE and neurobehavioral endpoints were also examined. MRL+/+ mice were exposed to 0.1 mg/ml TCE (~ 31 mg/kg/day) via maternal drinking water or direct exposure via the drinking water from gestation day 1 until postnatal day (PD) 42. TCE exposure did not impact gross motor skills but instead significantly altered social behaviors and promoted aggression associated with indicators of oxidative stress in brain tissues in male mice. The immunoregulatory effects of TCE involved a redox-associated promotion of T cell differentiation in the thymus that preceded the production of proinflammatory cytokines, IL-2, TNF-alpha, and IFN-gamma by mature CD4+ T cells. The results demonstrated that developmental and early life TCE exposure modulated immune function and may have important implications for neurodevelopmental disorders.
Blossom
Sarah J
SJ
Department of Pediatrics, University of Arkansas for Medical Sciences, College of Medicine, Arkansas Children's Hospital Research Institute, 1120 Marshall Street, Little Rock, AR 72202, USA. blossomsarah@uams.edu
Doss
Jason C
JC
Hennings
Leah J
LJ
Jernigan
Stefanie
S
Melnyk
Stepan
S
James
S Jill
SJ
D000818:Animals; D000831:Animals, Newborn; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006948:Hyperkinesis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D009422:Nervous System Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D012919:Social Behavior; D014241:Trichloroethylene / Q000633:toxicity*
D014241:Trichloroethylene