3,3',4,4'-Tetrachlorobiphenyl inhibits proliferation of immature thymocytes in fetal thymus organ culture.

Abstract

The environmental pollutant 3,3',4,4'-tetrachlorobiphenyl (TCB) leads to thymic atrophy and immunosuppression, 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 microM 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 microM TCB significantly reduced the total number of thymocytes, and fewer thymocytes were in S/G2M 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.