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.
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.
Urso
P
P
Department of Microbiology and Immunology, The Morehouse School of Medicine, Atlanta, GA 30310, USA. paul-urso@bellsouth.net
Wirsiy
Y G
YG
Zhang
W
W
Moolenaar-Wirsiy
P J
PJ
D000818:Animals; D000833:Animals, Suckling; D001564:Benzo(a)pyrene / Q000633:toxicity*; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000276:immunology; D004622:Embryo, Mammalian / Q000187:drug effects / Q000276:immunology; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000276:immunology; D008221:Lymphoid Tissue / Q000187:drug effects* / Q000276:immunology; D008297:Male; D018811:Maternal Exposure; D051379:Mice; D008809:Mice, Inbred C3H; D011247:Pregnancy; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D018800:Thy-1 Antigens / Q000096:biosynthesis; D014599:Uterus
D015704:CD4 Antigens; D016827:CD8 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; C078584:T-cell receptor V(gamma)3; D018800:Thy-1 Antigens; D001564:Benzo(a)pyrene