MyD88-silenced dendritic cells induce T-cell hyporesponsiveness and promote Th2 polarization in vivo.

ABSTRACT

BACKGROUND AIMS: Previous studies have determined that the absence of MyD88 enhances the tolerogenicity of dendritic cells (DCs), suggesting that inhibiting innate immunity may be a potential strategy to facilitate the induction of transplant tolerance by DCs. However, the underlying mechanism remains unclear. METHODS: Recipient rats were preconditioned with MyD88 gene-silenced DCs. In vivo distribution of infused MyD88 gene-silenced DCs in lymphatic organs was also analyzed. The response ability of recipient spleen T cells was determined by cell proliferation assay. The concentrations of interferon (IFN)-γ, interleukin (IL)-2, IL-4, IL-5 and IL-10 in cell culture supernates were measured with sandwich enzyme-linked immunosorbent assay. Flow cytometry was used to detect the transfection efficiency and CD4(+)CD25(+)FoxP3(+) T cell assay. RESULTS: After being infused into allogenic recipient rats, both MyD88-or control-silenced DCs were efficiently trafficked to the lymphatic organs and liver. The ex vivo analysis of proliferative responses revealed the donor-specific inhibition of alloimmune reactivity by MyD88-silenced DCs. This effect was associated with the marked inhibition of Th1-type cytokine production (IFN-γ and IL-2) but with significant promotion of Th2 type cytokine secretion (IL-4 and IL-5). CONCLUSIONS: It was demonstrated that T cells from recipients pretreated with MyD88-silenced DCs exhibited significantly reduced secretion of IFN-γ and IL-2 but markedly enhanced production of IL-4 and IL-5.