title: In vitro exposure to the herbicide atrazine inhibits T cell activation, proliferation, and cytokine production and significantly increases the frequency of Foxp3+ regulatory T cells.
abstract: The herbicide atrazine (2-chloro-4-[ethylamino]-6-[isopropylamino]-s-triazine) is the most common water contaminant in the United States. Atrazine is a phosphodiesterase inhibitor and is classified as an estrogen disrupting compound because it elevates estrogen levels via induction of the enzyme aromatase. Previous studies have shown that atrazine exposure alters the function of innate immune cells such as NK cells, DC, mast cells, and macrophages. In this study we have examined the impact of in vitro atrazine exposure on the activation, proliferation, and effector cytokine production by primary murine CD4(+) T lymphocytes. We found that atrazine exposure significantly inhibited CD4(+) T cell proliferation and accumulation as well as the expression of the activation markers CD25 and CD69 in a dose-dependent manner. Interestingly, the effects were more pronounced in cells from male animals. These effects were partially mimicked by pharmacological reagents that elevate intracellular cAMP levels and addition of exogenous rmIL-2 further inhibited proliferation and CD25 expression. Consistent with these findings, atrazine exposure during T cell activation resulted in a 2- to 5-fold increase in the frequency of Foxp3(+) CD4(+) T cells.
authors.affiliation: *Division of Biological Sciences, Center for Environmental Health Sciences and Department of Biomedical and Pharmaceutical Sciences, The University of Montana, Missoula, Montana 59812.
authors.forename: Lindsay E
authors.initials: LE
authors.lastname: Thueson
authors.affiliation: *Division of Biological Sciences, Center for Environmental Health Sciences and Department of Biomedical and Pharmaceutical Sciences, The University of Montana, Missoula, Montana 59812.
authors.forename: Tiffany R
authors.initials: TR
authors.lastname: Emmons
authors.affiliation: *Division of Biological Sciences, Center for Environmental Health Sciences and Department of Biomedical and Pharmaceutical Sciences, The University of Montana, Missoula, Montana 59812.
authors.forename: Dianna L
authors.initials: DL
authors.lastname: Browning
authors.affiliation: *Division of Biological Sciences, Center for Environmental Health Sciences and Department of Biomedical and Pharmaceutical Sciences, The University of Montana, Missoula, Montana 59812.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Kreitinger
authors.affiliation: *Division of Biological Sciences, Center for Environmental Health Sciences and Department of Biomedical and Pharmaceutical Sciences, The University of Montana, Missoula, Montana 59812.
authors.forename: David M
authors.initials: DM
authors.lastname: Shepherd
authors.affiliation: *Division of Biological Sciences, Center for Environmental Health Sciences and Department of Biomedical and Pharmaceutical Sciences, The University of Montana, Missoula, Montana 59812 *Division of Biological Sciences, Center for Environmental Health Sciences and Department of Biomedical and Pharmaceutical Sciences, The University of Montana, Missoula, Montana 59812 scott.wetzel@umontana.edu.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Wetzel
mesh_terms: D000818:Animals; D001280:Atrazine / Q000633:toxicity*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics*; D055879:Gene Knock-In Techniques; D006540:Herbicides / Q000633:toxicity*; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D020714:Maximum Tolerated Dose; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D013154:Spleen / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D006540:Herbicides; D007376:Interleukin-2; D000242:Cyclic AMP; D001280:Atrazine
keywords: CD4+ T cell; Foxp3; atrazine; cAMP; regulatory T cells