Regulatory Dendritic Cells Suppress Experimental Autoimmune Uveoretinitis in Mice

Abstract

Purpose:: To examine the potential effect of bone marrow-derived, mature, modified regulatory dendritic cells (rDCs) with potent immunoregulatory properties on the development of experimental autoimmune uveoretinitis (EAU) in mice.

Methods:: Murine bone marrow cells were treated in vitro with TGF-ß and IL-10, and then stimulated with lipopolysaccharide (LPS) to produce mature modified rDCs, and surface expression of major histocompatibility complex (MHC) molecules and costimulatory molecules were analyzed by flow cytometry. EAU was induced by immunizing C57BL/6 mice with human interphotoreceptor retinoid-binding protein peptide 1-20 (h-IRBP peptide), and rDCs (5 × 10⁶/mouse) were transferred intravenously to these mice on day 5 after immunization. Control EAU mice were injected with non-modified mature DC (mDCs) or PBS. Development of EAU was evaluated by clinical and histopathological examinations. Immunologic responses to h-IRBP peptide were assessed by delayed-type hypersensitibity (DTH) in vivo, and by antigen-specific T-cell proliferation and cytokine production (IFN-γ and IL-10) in vitro.

Results:: rDCs expressed moderately elevated expression levels of MHC molecules and low levels of costimulatory molecules (CD80, CD86 and CD40) compared to mDCs. Mice receiving rDCs developed very mild symptoms of EAU compared with control EAU mice receiving mDCs or PBS. Treatment with rDCs significantly suppressed the expression of delayed hypersensitivity responses to h-IRBP peptide. Antigen-specific T cell proliferative response, and IFN-γ production were significantly reduced and IL-10 was increased in DLN cells from rDC-treated mice compared to controls.

Conclusions:: Autologous rDCs may be a novel candidate of DC-based immunotherapy for human endogenous uveitis.

Keywords: uveitis-clinical/animal model • immune tolerance/privilege • immunomodulation/immunoregulation