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3, 3′, 4, 4′‐Tetrachlorobiphenyl Inhibits Proliferation of Immature Thymocytes in Fetal Thymus Organ Culture
Author(s) -
LAI ZW.,
KREMER J.,
GLEICHMANN E.,
ESSER C.
Publication year - 1994
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.1994.tb03403.x
Subject(s) - organ culture , fetus , biology , andrology , microbiology and biotechnology , endocrinology , medicine , pregnancy , biochemistry , genetics , in vitro
The environmental pollutant 3, 3′, 4, 4′‐tetrachlorobiphenyl (TCB) leads to thymic atrophy and immuno‐suppression, the former possibly causing the latter. TCB binds lo the cytosolic aryl‐hydrocarbon receptor (AhR) and transforms it into a DNA‐binding state. The development of fetal thymocyles 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 μM 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 μM 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 ihymocytes suggests that TCB enhanced thymocyte differentiation into mature CD8 + cells.