CELLULAR AND GENETIC-BASIS FOR SUPPRESSION OF CYTOTOXIC-T CELL GENERATION BY HALOAROMATIC HYDROCARBONS
CELLULAR AND GENETIC-BASIS FOR SUPPRESSION OF CYTOTOXIC-T CELL GENERATION BY HALOAROMATIC HYDROCARBONS
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DOI：
10.1016/0162-3109(83)90007-3
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发表时间：
1983-01-01
期刊：
影响因子：
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通讯作者：
GAULDIE, J
中科院分区：
文献类型：
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作者：
CLARK, DA;SWEENEY, G;GAULDIE, J
C57BL/6小鼠暴露于低剂量TCDD[2，3，7，8-四氯二苯并-对二恶英]后，其同种异体细胞毒性T细胞[CTL]的生成明显受到抑制。通过产生白介素2的能力来评估T辅助活性和CTL前体的频率在处理的动物中似乎不受影响，因此所描述的TCD诱导的抑制细胞是CTL反应减少的主要原因。抑制DBA/2小鼠CTL生成所需的剂量是C57B1/6小鼠的10~100倍，这与DBA/2小鼠的ah基因座基因(S)编码TCDD受体与TCDD低结合的观察结果一致。其他能够与TCDD受体结合的卤代芳烃(3，3‘’，4，4‘-四氯联苯和Aroclor 1254)也能抑制CTL的产生，而与TCDD受体缺乏亲和力的2，2’，4，4‘，6，6’-六氯联苯分子不抑制CTL的产生。TCDD对C57B/6和DBA/2小鼠的免疫毒性作用发生在低于诱导肝脏混合功能氧化酶所需的剂量水平。TCDD抑制CTL与增加对致死性II型疱疹病毒感染的易感性有关。低水平的TCDD可能与胸腺中TCDD的胞浆受体相互作用，并通过激活抑制细胞而诱导生物学意义上的免疫抑制。
Generation of allospecific cytotoxic T cells [CTL] in C57Bl/6 mice is significantly impaired following exposure to TCDD [2,3,7,8-tetrachlorodibenzo-p-dioxin] at doses as low as 4 ng/kg. T helper activity, as assessed by the ability to produce interleukin 2, and frequency of CTL precursors appear unaffected in treated animals and thus the TCCD-induced suppressor cells described are primarily responsible for the reduction in the CTL response. Suppression of CTL generation in DBA/2 mice requires a 10- to 100-fold greater dose than in C57B1/6, consistent with the observation that the Ah locus gene(s) of DBA/2 mice code for TCDD receptors with low binding affinity for TCDD. Other haloaromatic hydrocarbons (3,3''4,4''-tetrachlorobiphenyl and Aroclor 1254), capable of binding to the TCDD receptor, also suppress CTL generation, whereas the 2,2'',4,4'',6,6''-hexachlorobiphenyl molecule that lacks affinity for the TCDD receptor does not suppress CTL. The immunotoxic effects of TCDD in C57B/6 and DBA/2 mice occur at dose levels below those required to induce mixed-function oxidase enzymes in the liver. Suppression of CTL by TCDD is associated with increased susceptibility to lethal herpes virus type II infection. Low levels of TCDD may interact with cytoplasmic receptors for TCDD in the thymus and induce biologically significant immunosuppression through activation of suppressor cells.