MODULATION OF T-CELL ONTOGENY BY TRANSPLACENTAL BENZO(A)PYRENE

Transplacental exposure to the carcinogen, benzo(a)pyrene BaP, leads t o depressed immune function and increased tumor incidence in mice. Thi s paper reports ontogenetic T-cell changes in BALB/c mice after exposu re to BaP in utero. Monoclonal antibodies (MAbs) were produced to feta l liver T-cells (FLT) and newborn spleen (NBS) lymphocytes purified fr om 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 rea cted with two T-cell membrane antigens (FLT and NBS) found in fetal li ver, neonataI and adult thymus and spleen. Lymphocytes of BaP-exposed 19-day fetuses showed decreased subpopulation frequencies (P<0.05) in fetal liver total T-ceIls (from 56% to 16%), Lyl 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 relati ve resistance to BaP toxicity and/or BaP-enhanced proliferation in the neonatal period. Compared with untreated controls, BaP treatment resu lted in reduced numbers of T-cells in fetal liver and showed a selecti ve toxicity for Lyl 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 de pletion (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 t his 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 pro geny exposed to BaP in utero.