Modulation of T-cell ontogeny by transplacental benzo(a)pyrene.
Transplacental exposure to the carcinogen, benzo(a)pyrene BaP, leads to depressed immune function and increased tumor incidence in mice. This paper reports ontogenetic T-cell changes in BALB/c mice after exposure to BaP in utero. Monoclonal antibodies (MAbs) were produced to fetal liver T-cells (FLT) and newborn spleen (NBS) lymphocytes purified from offspring of pregnant BALB/c mice that were given one injection of BaP (150 mg/kg body weight) in mid-gestation (day 11-13). The MAbs reacted with two T-cell membrane antigens (FLT and NBS) found in fetal liver, neonatal and adult thymus and spleen. Lymphocytes of BaP-exposed 19-day fetuses showed decreased subpopulation frequencies (P < 0.05) in fetal liver total T-cells (from 56% to 16%), Ly1 cells (from 33% to 9%), and Ly2 cells (from 56% to 1%) compared with untreated controls. In contrast, BaP increased the subpopulation frequencies (P < 0.05) in FLT cells in fetal liver (from 20% to 52%) and in newborn spleen (from 21% to 51%), and increased NBS cells in newborn spleen (from 24% to 59%). The increased frequency in FLT and NBS cells was due to their relative resistance to BaP toxicity and/or BaP-enhanced proliferation in the neonatal period. Compared with untreated controls, BaP treatment resulted in reduced numbers of T-cells in fetal liver and showed a selective toxicity for Ly1 cells (89% reduction) and Ly2 cells (99% reduction), whereas FLT cells were not reduced and NBS cells were reduced by 60%. Six-week-old juvenile mice exposed to BaP in utero showed recovery of total T-cells to control levels in spleen and thymus, but showed depletion (P < 0.01) in thymic FLT cells (from 81% to 12%) and in splenic NBS cells (from 55% to 16%). The monoclonal antibodies developed for this study recognize novel cellular changes in the murine immune system that are associated with transplacental BaP. The FLT and NBS antigens may be useful biomarkers for developmental immune dysfunctions in progeny exposed to BaP in utero.
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National Institute for Occupational Safety and Health, Centers for Disease Control, Cincinnati, OH 45226-1998, USA.
Henningsen
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D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis / Q000276:immunology*; D001564:Benzo(a)pyrene / Q000493:pharmacokinetics / Q000633:toxicity*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D005315:Fetal Diseases / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D007153:Immunologic Deficiency Syndromes / Q000139:chemically induced* / Q000151:congenital / Q000196:embryology / Q000473:pathology; D008099:Liver / Q000196:embryology / Q000276:immunology / Q000473:pathology; D008212:Lymphocyte Depletion; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D013154:Spleen / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000196:embryology / Q000276:immunology / Q000473:pathology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D001564:Benzo(a)pyrene