Exposure to tetrachlorodibenzo-p-dioxin (TCDD) alters fetal thymocyte maturation.
We previously reported that thymic atrophy and reduced thymic cellularity associated with prenatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice are characterized by quantitative alerations in the number of thymocytes expressing CD4 and CD8 surface antigens. In the present study, these observations have been extended to establish the specific thymocyte maturation processes affected by TCDD through an examination of cell size distributions, alpha beta and gamma delta T cell receptor (TCR) expression, peanut agglutinin (PNA) binding, and J11d marker analysis in murine thymocytes exposed prenatally to TCDD. Pregnant mice were administered vehicle, 1.5 or 3.0 micrograms/kg body wt TCDD by gavage on gestational Days (gd) 6-14. Flow cytometry analysis of gd 18 fetal thymocytes revealed a reduction in the number of small CD4+CD8+ double positive (DP) and PNA+, small thymocytes in the TCDD-exposed groups. The large cell population was reduced by TCDD to approximately 70% of control values. There was also a significant shift in TCR expression of thymocytes with a decrease in alpha beta TCR and a concommitant increase in gamma delta TCR expression from TCDD-exposed fetuses. The CD4-CD8+J11d+ thymocytes were increased in TCDD-treated mice while the more mature CD4-CD8+J11d- thymocyte numbers were similar to controls. Taken together, these data indicate that TCDD inhibits thymocyte maturation at the transition phase between the CD4-CD8+J11d+ phenotype and the DP/J11d+ thymocytes.
Blaylock
B L
BL
Immunotoxicology Group, Systems Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Holladay
S D
SD
Comment
C E
CE
Heindel
J J
JJ
Luster
M I
MI
D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology; D051927:CD24 Antigen; D015704:CD4 Antigens / Q000502:physiology; D016516:CD4-CD8 Ratio; D016827:CD8 Antigens / Q000502:physiology; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000276:immunology; D005260:Female; D037102:Lectins / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D019887:Peanut Agglutinin; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011247:Pregnancy; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects / Q000502:physiology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000187:drug effects / Q000502:physiology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000187:drug effects / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000196:embryology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D051927:CD24 Antigen; D015704:CD4 Antigens; D016827:CD8 Antigens; C497890:Cd24a protein, mouse; D037102:Lectins; D008562:Membrane Glycoproteins; D019887:Peanut Agglutinin; D000072317:Polychlorinated Dibenzodioxins; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta