OP0194 IMMUNOSUPPRESSIVE EFFECT OF TOLEROGENIC DENDRITIC CELLS ON AUTOLOGOUS T-CELLS IN PATIENTS WITH RHEUMATOID ARTHRITIS

Abstract

Background:Dendritic cells (DCs) are known to contribute to the pathogenesis of rheumatoid arthritis (RA) through presentation of cartilage glycoprotein, production of proinflammatory cytokines and activation of Th1/Th17 responses. Along with stimulating activity, DCs may exhibit suppressive functions via capacity to induce T cell apoptosis/anergy and to generate regulatory T cells. Since these DCs have potential to control autoreactive T-lymphocytes, the enhancing of tolerogenic properties of DCs seems to be a new important strategy in treatment of RA. However, it remains unclear whether autoreactive T lymphocytes are sensitive to the immunosuppressive effects of DC.Objectives:The aim of our study is to investigate the mechanisms of the inhibitory effect of dexamethasone-modified DCs (dexDCs) in patients with RA on autologous T cells.Methods:Twenty patients with RA with high and moderate activity of disease were recruited in this study. All patients fullfield ACR/EULAR criteria (2010). All studies were performed after receiving informed consent. DCs were generated from blood monocytes culturing for 5 days with GM-CSF and IFN-α in the presence dexamethasone, applied on third day. LPS as maturation stimuli was added on fourth day. The study evaluated the ability of dexDCs to induce T cell apoptosis, inhibit the production of Th1 and Th17 cytokines in auto-mixed leukocytes culture (MLC), induce the activation of T-regulatory cells, and inhibit the purified protein derivative (PPD)-specific immune response.Results:We revealed that dexDCs markedly suppressed the production of IFN-γ and IL-17, while the decreasing of IL-4 and IL-13 was less pronounced. Thus, in comparison with Th2 cells, Th1 and Th17 T lymphocytes were more sensitive to suppressor effects of dexDCs. We also revealed a significant increasing of cells in the stage of late apoptosis (An+Pi+) during the cultivation of autologous T cells with dexDCs. We have also proved the suppressive effect of dexDCs on culture T cells that are co-cultivated with mature DCs (reduction of proliferation from 2700 cpm to 1500 cpm, p=0.0015). In addition, we have shown the ability of dexDCs to induce T-regulatory cells with a phenotype CD4+IL10+Tr1. In conclusion, we have shown the ability of PPD-loaded dexDCs to inhibit the proliferative response of both mature DCS and mature dexDCs-loaded PPD, that indicates the ability of dexDCs to possess antigen-specific suppression.Conclusion:The data obtained indicate that, dexDCs from RA patients have an immunosuppressive effect on autologous T cells through the induction of apoptosis, anergia and activation of T regulatory cells that authorise their application as a DCs-vaccine.Disclosure of Interests:None declared