title: Propanil exposure induces delayed but sustained abrogation of cell-mediated immunity through direct interference with cytotoxic T-lymphocyte effectors.
abstract: The postemergent herbicide propanil (PRN ; also known as 3,4-dichloropropionanilide) is used on rice and wheat crops and has well-known immunotoxic effects on various compartments of the immune system, including T-helper lymphocytes, B lymphocytes, and macrophages. It is unclear, however, whether PRN also adversely affects cytotoxic T lymphocytes (CTLs) , the primary (1 degrees ) effectors of cell-mediated immunity. In this study we examined both the direct and indirect effects of PRN exposure on CTL activation and effector cell function to gauge its likely impact on cell-mediated immunity. Initial experiments addressed whether PRN alters the class I major histocompatibility complex (MHC) pathway for antigen processing and presentation by antigen-presenting cells (APCs) , thereby indirectly affecting effector function. These experiments demonstrated that PRN does not impair the activation of CTLs by PRN-treated APCs. Subsequent experiments addressed whether PRN treatment of CTLs directly inhibits their activation and revealed that 1 degrees alloreactive CTLs exposed to PRN are unimpaired in their proliferative response and only marginally inhibited in their lytic activity. Surprisingly, secondary stimulation of these alloreactive CTL effectors, however, even in the absence of further PRN exposure, resulted in complete abrogation of CTL lytic function and a delayed but significant long-term effect on CTL responsiveness. These findings may have important implications for the diagnosis and clinical management of anomalies of cell-mediated immunity resulting from environmental exposure to various herbicides and other pesticides.
authors.affiliation: Department of Microbiology, Immunology, and Cell Biology, West Virginia University School of Medicine, Morgantown, West Virginia, USA. jsheil@hsc.wvu.edu
authors.forename: James M
authors.initials: JM
authors.lastname: Sheil
authors.forename: Marc A
authors.initials: MA
authors.lastname: Frankenberry
authors.forename: Todd D
authors.initials: TD
authors.lastname: Schell
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Brundage
authors.forename: John B
authors.initials: JB
authors.lastname: Barnett
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019343:Citric Acid / Q000494:pharmacology; D005260:Female; D006540:Herbicides / Q000494:pharmacology*; D051379:Mice; D011411:Propanil / Q000008:administration & dosage* / Q000494:pharmacology* / Q000633:toxicity; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology*
chemical_list: D006540:Herbicides; D019343:Citric Acid; D011411:Propanil