Immunotoxicity of endocrine disruptors

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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.