3,3',4,4'-TETRACHLOROBIPHENYL INHIBITS PROLIFERATION OF IMMATURE THYMOCYTES IN FETAL THYMUS ORGAN-CULTURE

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