EVIDENCE FOR DIRECT ACTION OF 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN (TCDD) ON THYMIC EPITHELIUM
EVIDENCE FOR DIRECT ACTION OF 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN (TCDD) ON THYMIC EPITHELIUM
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DOI：
10.1016/0041-008x(85)90373-4
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发表时间：
1985-01-01
影响因子：
3.8
通讯作者：
OSBORNE, R
中科院分区：
文献类型：
--
作者：
GREENLEE, WF;DOLD, KM;OSBORNE, R
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) acts on selected targets within the immune system to produce a characteristic profile of pathologic responses typified by thymic atrophy, suppressed cellular immunity and inhibition of antibody production to T-lymphocyte-dependent antigens. Studies in inbred mice differing in sensitivity to TCDD indicate that TCDD-induced thymic atrophy was mediated by a receptor protein (designated the Ah receptor). To study the cellular and molecular basis for TCDD-induced thymic atrophy, primary cultures of thymic epithelial (TE) cells were established from C57BL/6 mice, a strain sensitive to TCDD. Treatment of TE monolayers with TCDD (0.1-10 nM) resulted in the altered maturation of cocultured syngeneic thymocytes as judged by suppression (40% of control at 10 nM TCDD) of TE-dependent responsiveness of thymocytes to the mitogens concanavalin A and phytohemagglutinin. TE-conditioned medium enhanced the mitogen responsiveness of thymocytes 3- to 4-fold; the enhanced mitogen response mediated by the TE-conditioned medium was not suppressed in thymocytes incubated in medium collected from TCDD-treated cultures or in TE-conditioned medium to which TCDD (10 nM) had been added directly. The suppression of TE-dependent maturation of thymocytes was concentration dependent (EC50 .apprx. 1 nM) and stereospecific, suggesting involvement of the Ah receptor. The Ah receptor in cytosol fractions from cultured TE cells was measured directly and was found to be present at a concentration 3 and 3.5-fold greater than that measured in whole thymus and thymocytes, respectively. TCDD acted directly on epithelial target cells in the thymus. One consequence of this action appeared to be the altered thymus-dependent maturation of T-lymphocyte precursors, mediated through direct cell-cell contact between thymocytes and TE cells.
