Impairment of prothymocyte activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Impairment of prothymocyte activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
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DOI：
10.4049/jimmunol.144.4.1169
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发表时间：
1990-02
影响因子：
4.4
通讯作者：
J. S. Fine;A. Silverstone;T. Gasiewicz
中科院分区：
文献类型：
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作者：
J. S. Fine;A. Silverstone;T. Gasiewicz
实验动物暴露于2，3，7，8-四氯二苯并-对-二恶英（TCDD）可导致严重的胸腺萎缩和细胞介导的和体液免疫功能的抑制。然而，尽管做了很多努力，TCDD产生这些反应的机制，特别是胸腺萎缩，仍然不清楚。在这份报告中，我们研究了急性TCDD暴露对年轻成年BALB/c小鼠的淋巴细胞干细胞的影响，以确定T淋巴细胞生成早期事件的改变是否有助于TCDD诱导的胸腺萎缩。TCDD单次给药5 - 120微克/千克后，胸腺重量和细胞结构呈剂量依赖性降低。这种胸腺萎缩与骨髓和胸腺中淋巴细胞干细胞特异性DNA聚合酶末端脱氧核苷酸转移酶的生物合成和mRNA水平的剂量依赖性抑制相关。然而，胸腺末端脱氧核苷酸转移酶合成的减少，在每个细胞的基础上，是小于在骨髓中观察到的。胸腺内CD 4/CD 8和IL-2 R表达仅表现出轻微的变化后，暴露于30微克TCDD/kg。这些数据表明，胸腺细胞是更难治TCDD比前T细胞。为了直接评估这种可能性，TCDD处理的供体小鼠的骨髓前胸腺细胞进行了检查，以确定其重建过继性辐射受体胸腺的能力。我们的研究结果表明，前胸腺细胞的活动受到严重损害的TCDD曝光，这种影响发生在低组织水平的TCDD。相反，我们观察到集落形成单位-粒细胞-巨噬细胞的数量没有减少，而集落形成单位-脾脏的数量中度减少。这些数据表明，TCDD诱导的胸腺萎缩的结果，至少在一定程度上，受损的胸腺播种由prothymocytes。
Exposure of experimental animals to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) results in severe thymic atrophy and suppression of cell-mediated and humoral immune functions. However, despite much effort the mechanism by which TCDD produces these responses, particularly thymic atrophy, remains unclear. In this report, we have examined the effect of acute TCDD exposure on lymphocyte stem cells in young adult BALB/c mice to determine whether alterations to events early in T lymphopoiesis contribute to TCDD-induced thymic atrophy. TCDD produced a dose-dependent reduction in thymic weight and cellularity following a single dose of 5 to 120 micrograms TCDD/kg. This thymic atrophy correlated with a dose-dependent suppression of the biosynthesis and mRNA levels of the lymphocyte stem cell-specific DNA polymerase terminal deoxynucleotidyl transferase in bone marrow and thymus. However, the reduction in thymic terminal deoxynucleotidyl nucleotidyl transferase synthesis, on a per cell basis, was less than that observed in bone marrow. Intrathymic CD4/CD8 and IL-2R expression demonstrated only mild alterations after exposure to 30 micrograms TCDD/kg. These data suggest that thymocytes are more refractory to TCDD than are pre-T cells. To assess this possibility directly, bone marrow prothymocytes from TCDD-treated donor mice were examined for their capacity to reconstitute the thymuses of adoptive, irradiated recipients. Our results indicate that prothymocyte activity was severely impaired by TCDD exposure and that this effect occurred at low tissue levels of TCDD. In contrast, we observed no reduction in the number of colony-forming unit-granulocyte macrophage and a moderate decrease in colony-forming unit-spleen. These data suggest that TCDD-induced thymic atrophy is the result, at least in part, of impaired thymic seeding by prothymocytes.