Chronic exposure to water pollutant trichloroethylene increased epigenetic drift in CD4(+) T cells.
Autoimmune disease and CD4(+) T-cell alterations are induced in mice exposed to the water pollutant trichloroethylene (TCE). We examined here whether TCE altered gene-specific DNA methylation in CD4(+) T cells as a possible mechanism of immunotoxicity.



Naive and effector/memory CD4(+) T cells from mice exposed to TCE (0.5 mg/ml in drinking water) for 40 weeks were examined by bisulfite next-generation DNA sequencing.



A probabilistic model calculated from multiple genes showed that TCE decreased methylation control in CD4(+) T cells. Data from individual genes fitted to a quadratic regression model showed that TCE increased gene-specific methylation variance in both CD4 subsets.



TCE increased epigenetic drift of specific CpG sites in CD4(+) T cells.
Departments of Microbiology & Immunology, & Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock, AR 72202, USA.
Kathleen M
KM
Gilbert
Departments of Microbiology & Immunology, & Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock, AR 72202, USA.
Sarah J
SJ
Blossom
Departments of Microbiology & Immunology, & Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock, AR 72202, USA.
Stephen W
SW
Erickson
College of Engineering, Colorado State University, Fort Collins, CO 80523, USA.
Brad
B
Reisfeld
College of Engineering, Colorado State University, Fort Collins, CO 80523, USA.
Todd J
TJ
Zurlinden
Departments of Microbiology & Immunology, & Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock, AR 72202, USA.
Brannon
B
Broadfoot
Departments of Microbiology & Immunology, & Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock, AR 72202, USA.
Kirk
K
West
Departments of Microbiology & Immunology, & Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock, AR 72202, USA.
Shasha
S
Bai
Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, USA.
Craig A
CA
Cooney
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D018899:CpG Islands; D019175:DNA Methylation; D004781:Environmental Exposure; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005260:Female; D051379:Mice; D014241:Trichloroethylene / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D014874:Water Pollutants, Chemical; D014241:Trichloroethylene
CD4+ T cells; DNA methylation; IFN-γ; autoimmunity; immunotoxicity; next generation sequencing; quadratic regression; trichloroethylene