Alterations in CD4+, CD8+, Vgamma3, Vgammadelta, and/or Valpha betaT-lymphocyte expression in lymphoid tissues of progeny after in utero exposure to benzo(alpha)pyrene.J Immunotoxicol. 2008 Jul; 5(3):293-306.JI
That benzo alpha)pyrene (Balpha P) decreases both humoral and cell-mediated immunity, and leads to increases in progeny tumor development after in utero insult, suggests that T- and B-lymphocytes are made defective in exposed offspring. In the study here, C3H mice were injected once with Balpha P (150 microg/g BW) at day 12 of pregnancy and progeny lymphoid tissues were excised during gestation (day 18; GD18) or at 1 or 6 weeks post-partum. The isolated lymphoid cells were analyzed by flow cytometry/immunofluorescence or assessed for function. In Balpha P-exposed fetuses, thymic Thy1(+) cell levels were decreased (relative to levels in organs of corn oil-exposed dam progeny). In addition, for up to 6 weeks post-birth, CD4(+)CD8(+) (double positive; DP) cells were virtually absent and levels of CD4(-)CD8(-) (double negative; DN) cells were consistently at epsilon 90%. With regard to single positive (SP) cells, CD4(+) cell levels were also decreased in tissues at GD18 up through 6 weeks post-birth; CD8(+) cell levels were increased, but only in pups at 1-week and 6-weeks post-birth. In 1-week-old progeny, spleen CD8(+) cell levels were quantitatively unchanged, though CD4(+) levels were reduced 2-4-fold and CD4(-)CD8(-) DN levels significantly increased. With respect to TCRs, fetal levels of thymic CD3Vgamma(3)(+) and CD3Vgamma delta(+) cells were decreased; levels of CD3Valphabeta cells were only slightly depressed. The latter results contrast sharply with a strong reduction in CD3Valphabeta cells in the fetal livers of Balpha P-exposed progeny. Interestingly, these livers also strongly evidenced a presence of BalphaP-7,8-dihydrodiol-9,10-epoxide metabolite. When assessed for any change in function, the CD4(+), Thy1(+) cells isolated from Balpha P-exposed progeny tissues responded weakly (relative to controls) to ConA and in an allogeneic MLR. Taken in totality, the results here strengthen our original hypothesis that BalphaP can create a favorable milieu for tumor growth progression in progeny of exposed mothers by affecting development of sufficient numbers of functional lymphocytes in the offspring.