414 Induction of il-17 production from human peripheral blood cd4+ cells by asbestos exposure

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From our previously reports, chronic, recurrent and low-dose exposure to asbestos fibres causes a reduction in antitumor immunity. In addition with natural kileer (NK) cells and cytotoxic T lymphocytes (CTL), the analysis of T helper cells showed that surface CXCR3, chemokine receptor, and the productive potential of interferon (IFN)γ were reduced following asbestos exposure in an in vitro cell line model and in peripheral CD4 +cells of asbestos-exposed patients. Moreover, experiments revealed that asbestos exposure enhanced regulatory T cell (Treg) function. This study also focused on CXCR3 expression and the Th-17 cell fraction. Following activation with T-cell receptor and co-culture with various concentrations of chrysotile fibres using freshly isolated CD4 +surface CXCR3 positive and negative fractions, the intracellular expression of CXCR3, IFNγ and IL-17 remained unchanged when co-cultured with chrysotile. However, subsequent re-stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin resulted in enhanced IL-17 production and expression, particularly in CD4 +surface CXCR3 positive cells. These results indicated that the balance and polarisation between Treg and Th-17 fractions play an important role with respect to the immunological effects of asbestos and the associated reduction in antitumor immunity.

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