Induction of T Regulatory Cells Using Populations of Differentially Activated Dendritic Cells in Experimental Autoimmune Uveitis (EAU)

Abstract

Abstract: : Purpose: Previous studies of dendritic cell vaccination in the model of EAU show that immature dendritic cells, primed with Interphotoreceptor Binding Protein (IRBP) induce tolerance while mature dendritic cells prime the immune response. More recently these distinctions have become blurred and dendritic cell populations may variously induce suppression of immunity depending on the conditions. The aim of this study is to investigate the conditions which best promote induction of T regulatory cells by dendritic cells Methods: CD4+CD25+ regulatory T cells (T reg) were isolated from the cervical lymph nodes three days after inoculation with LPS treated, IRBP primed dendritic ells. FoxP3 expression was semiquantitativley analysed by RT PCR. IL10 production was assayed by intracellular staining on flow cytometry. T reg function was investigated in vitro by transwell experiments. Results: Early administration of LPS to mature DCs significantly affected FoxP3 expression in the CD4+CD25+ T reg population. However, this was not associated with a change in IL10 production. T reg function appeared to be cell– contact dependent. Inhibition of EAU was inducible under certain conditions of LPS exposure to dendritic cells where apparent maturation of the cells might be expected. Conclusions: Dendritic cells are important in driving the immune response towards disease or tolerance. These data suggest that antigen primed, matured DC’s enhance CD4+25+ Treg induction. However the role of FoxP3 in our model for immunosuppressive properties is not yet clear.

Keywords: autoimmune disease • uveitis-clinical/animal model