3, 3′, 4, 4′-Tetrachlorobiphenyl Inhibits Proliferation of Immature Thymocytes in Fetal Thymus Organ Culture

作者: Z-W. LAI , J. KREMER , E. GLEICHMANN , C. ESSER

DOI: 10.1111/J.1365-3083.1994.TB03403.X

关键词:

摘要: The environmental pollutant 3,3',4,4'-tetrachlorobiphenyl (TCB) leads to thymic atrophy and immunosuppression, the former possibly causing latter. TCB binds cytosolic aryl-hydrocarbon receptor (AhR) transforms it into a DNA-binding state. development of fetal thymocytes is severely affected by other AhR-binding xenobiotics, leading skewed pattern thymocyte maturation stages. Murine proliferation after exposure was studied in thymus organ culture (FTOC). C57BL/6 fetus lobes from day 15 gestation were explanted grown for 2, 4, 6, 8 days presence or absence 3.3 microM TCB. Subsets defined CD4 CD8 surface markers, their cell cycle analysed DNA staining with 7-amino-actinomycin D (7-AAD). Exposure thymi vitro significantly reduced total number thymocytes, fewer S/G2M phase. inhibition induced treatment mainly CD4-CD8- (double-negative, DN) CD4-CD8+ (single-positive, SP) subsets, these appeared more immature i.e. DNCD3- CD8+CD3- subpopulations, whereas no effect on CD4+CD8+ (double-positive, DP) proliferative activity observed. Analysis relation subsets differentiating suggests that enhanced differentiation mature CD8+ cells.

参考文章(50)
T A Gasiewicz, A E Silverstone, J S Fine, Impairment of prothymocyte activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Journal of Immunology. ,vol. 144, pp. 1169- 1176 ,(1990)
D. McConkey, P Hartzell, S. Duddy, H Hakansson, S Orrenius, 2,3,7,8-Tetrachlorodibenzo-p-dioxin kills immature thymocytes by Ca2+-mediated endonuclease activation. Science. ,vol. 242, pp. 256- 259 ,(1988) , 10.1126/SCIENCE.3262923
S. D. Holladay, P. Lindstrom, B. L. Blaylock, C. E. Comment, D. R. Germolec, J. J. Heindell, M. I. Luster, Perinatal thymocyte antigen expression and postnatal immune development altered by gestational exposure to tetrachlorodibenzo-p-dioxin (TCDD) Teratology. ,vol. 44, pp. 385- 393 ,(1991) , 10.1002/TERA.1420440405
Mark Egerton, Ken Shortman, Roland Scollay, The kinetics of immature murine thymocyte development in vivo. International Immunology. ,vol. 2, pp. 501- 507 ,(1990) , 10.1093/INTIMM/2.6.501
T. Sutter, K Guzman, K. Dold, W. Greenlee, Targets for dioxin: genes for plasminogen activator inhibitor-2 and interleukin-1 beta. Science. ,vol. 254, pp. 415- 418 ,(1991) , 10.1126/SCIENCE.1925598
M Blackman, J Kappler, P Marrack, The role of the T cell receptor in positive and negative selection of developing T cells Science. ,vol. 248, pp. 1335- 1341 ,(1990) , 10.1126/SCIENCE.1972592