Effects of 2,3,7,8-TCDD and PCB 126 on human thymic epithelial cells in vitro.
2,3,7,8-Tetrachloro-dibenzo- p-dioxin (TCDD) is a ubiquitously distributed xenobiotic. The adverse effects of TCDD on the mammalian immune system have been studied for decades, but it is still unclear whether TCDD has direct effects on T-lymphocytes or whether it acts via the thymic microenvironment. We have studied the effects of TCDD on primary cultures of human thymic epithelial cells (TEC) focusing on differentiation markers, integrins and adhesion molecules involved in cell-cell and in cell-matrix interactions. TEC were treated with TCDD at concentrations of 0.001, 0.01, 0.1, 1.0 or 10.0 nM or with 100 nM PCB 126 (3,3',4,4',5-pentachlorobiphenyl) for 3 days, and were then analysed by flow cytometry for expression of surface antigens using monoclonal antibodies against Hassall's bodies (TE-8, TE-16) or against surface structures such as CD29, CD49b, CD49e, CD49f, CD51, CD54, CD58, CD61 and CD106. At TCDD concentrations as low as 0.01 nM we found a significant increase in terminally differentiated, TE-16-positive TEC; at a ten-fold greater concentration the number of cells marked with the TE-8 antibody was also increased. With both markers the most pronounced effect (approximately +15%) was observed at 1 nM TCDD. An increase of cells expressing the integrin alpha-chains CD49b, CD49e and CD51 as well as CD54 was observed at concentrations of 0.1 nM TCDD or higher. The proportion of cells expressing CD106 or CD49f decreased significantly upon treatment with TCDD. No effects on the integrin beta-chains CD29 and CD61 could be detected. Overall, PCB 126 induced similar changes to TCDD. In summary, TCDD and a coplanar PCB induced terminal differentiation of human TEC along with changes of integrins and other adhesion molecules. These receptors and their interplay with the extracellular matrix have key functions in the maturation of T-lymphocytes and it is plausible that their alteration would be involved in TCDD-induced immunotoxicity.
Riecke
Kai
K
Institut für Klinische Pharmakologie und Toxikologie (Abt. Toxikologie), Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Garystrasse 5, 14195, Berlin, Germany.
Schmidt
André
A
Stahlmann
Ralf
R
D015703:Antigens, CD / Q000096:biosynthesis; D000943:Antigens, Differentiation / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002450:Cell Communication; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D039001:Integrin alpha Chains / Q000096:biosynthesis; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D015703:Antigens, CD; D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules; D039001:Integrin alpha Chains; D000072317:Polychlorinated Dibenzodioxins; D011078:Polychlorinated Biphenyls; C023035:3,4,5,3',4'-pentachlorobiphenyl