Persistent suppression of contact hypersensitivity, and altered T-cell parameters in F344 rats exposed perinatally to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
The outcome of perinatal low-level TCDD exposure on the T-cell-mediated contact hypersensitivity (CHS) response in adult F344 rats was investigated. Suppression of the 2,4-dinitrofluorobenzene (DNFB)-specific contact hypersensitivity reponse occurred in mature offspring of dams dosed by gavage with 1microg or 3microg TCDD/kg on gestation day (GD) 14. To determine if this effect was correlated with altered distribution or activation of major T-cell subtypes, cells of the auricular lymph node draining the hapten-treated skin were evaluated by flow cytometry for expressed phenotype, including activation markers, 24h after challenge. Six-month-old female offspring with significantly decreased CHS and born to dams given 3microg TCDD/kg, had significantly greater proportion of CD4(+) T cells expressing a naive phenotype marker, CD45RC(hi), in their draining nodes. The greater relative frequency of this CD4(+) subset in peripheral lymphoid tissues associated with a reduced CHS in these rats may be attributed to a reduction in the proportion of CD4(+) T cells maintaining or recruited into an activated state. The CHS proved to be a valuable bioassay for investigating long-term immunotoxic effects of perinatal TCDD exposure in rats.
Walker
Dana B
DB
Wyeth Research, 641 Ridge Road, Chazy, NY 12921, USA. walkerd4@wyeth.com
Williams
Wanda C
WC
Copeland
Cary B
CB
Smialowicz
Ralph J
RJ
D000284:Administration, Oral; D000818:Animals; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000002:abnormalities / Q000187:drug effects*; D005434:Flow Cytometry; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008297:Male; D018811:Maternal Exposure; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011916:Rats, Inbred F344; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D017493:Leukocyte Common Antigens