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 t he latter. TCB binds to the cytosolic aryl-hydrocarbon receptor (AhR) and transforms it into a DNA-binding state. The development of fetal t hymocytes is severely affected by TCB and other AhR-binding xenobiotic s, leading to a skewed pattern of thymocyte maturation stages. Murine thymocyte proliferation after exposure to TCB was studied in fetal thy mus organ culture (FTOC). C57BL/6 fetus thymic lobes from day 15 of ge station were explanted and grown for 2, 4, 6, and 8 days in organ cult ure 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 tota l number of thymocytes, and fewer thymocytes were in S/G(2)M phase. Th e inhibition of cell proliferation induced by TCB treatment affected m ainly the CD4(-)CD8(-) (double-negative, DN) and CD4(-)CD8(+) (single- positive, SP) subsets, and these inhibition appeared mainly in more im mature thymocytes, i.e. DNCD3(-) and CD8(+) CD3(-) subpopulations, whe reas no effect of TCB on CD4(+)CD8(+) (double-positive, DP) cell proli ferative activity was observed. Analysis of the relation of cell proli feration and development of subsets in differentiating fetal thymocyte s suggests that TCB enhanced thymocyte differentiation into mature CD8 (+) cells.