Immunotoxicity of endocrine disruptors

已有研究表明，较高剂量的三丁基锡(TBT)通过诱导T细胞凋亡而产生免疫毒性作用，如胸腺萎缩。然而，环境相关剂量的TBT对免疫反应的影响仍不清楚。在本研究中，我们发现0.01CD3MTBT在未诱导μ~+T细胞明显凋亡的情况下，通过抑制和促进抗CD3T细胞和脾抗原提呈细胞(APC)诱导的初始CD4T细胞的Th1和Th2的形成，促进了Th2型细胞的极化。在平板包被抗CD3+抗CD28的原代培养中，未观察到TBT诱导的Th2极化。TBT分别抑制和增强脾APC与初始CD4+T细胞相互作用产生的IL-12和IL-10。加入IL-12或抗IL-10或去除B细胞后，TBT引起的Th2极化增强可被消除。综上所述，TBT对Th2极化的促进作用可能与其抑制巨噬细胞/DC产生IL-12，促进B细胞产生IL-10有关。30μ摩尔/kgTBT处理组、卵清蛋白免疫组和巴西新城疫原虫感染组小鼠的Th2细胞也有明显的极化。我们的结果表明，TBT可能通过促进Th2偏离而导致变态反应性疾病的发生。

It has been shown that relatively high doses of tributyltin (TBT) exerts immunotoxic effects such as thymic atrophy via induction of apoptosis in T cells. However, the effect of environmentally relevant doses of TBT on the immune responses remains to be unknown. Here we show that 0.01-0.1 μM TBT, at which no obvious apoptosis was induced in CD4^+ T cells, promoted strong Th2 polarization via suppression and augmentation of Th1 and Th2 development, respectively, from naive CD4+ T cells primed with anti-CD3 and splenic antigen presenting cells (APC). TBT-induced Th2 polarization was not observed in the primary cultures driven by plate coated anti-CD3 plus anti-CD28. Production of IL-12 and IL-10 by splenic APC interacting with naive CD4^+ T cells was suppressed and augmented, respectively, by TBT. Addition of IL-12 or anti-IL-10, or depletion of B cells in splenic APC population resulted in the abrogation of enhanced Th2 polarization induced by TBT. Taken together, these results suggest that promotion of Th2 polarization induce by TBT could be due to the suppression of IL-12 production of macrophages/DC and augmentation of IL-10 production of B cells. Th2 polarization was also induced in mice treated with 30 μmole/kg TBT and immunized with OVA or infected with N. brasiliensis. Our results suggest that TBT may present significant risk for the induction of allergic diseases via promotion of Th2 deviation.