Tolerogenic Dendritic Cells in Experimental Autoimmune Encephalomyelitis as a Tool before Its Translation to MS Patients (P05.171)

OBJECTIVE: The aim of this study was to generate bone marrow derived tolDCs (BM-tolDCs) from C57BL/6 mice loaded with Myelin Oligodendrocyte Glycoprotein (MOG)40-55 peptid and define their capability to inhibit specific proliferation of splenocytes of mice with EAE. BACKGROUND: Specific cell therapy with tolerogenic Dendritic Cells (tolDCs) loaded with autoantigens is a promising tool for the attenuation of pathogenic T cells in autoimmune diseases such as Multiple Sclerosis (MS). Before its translation to patients, it is important to better characterize its efects on the EAE model. DESIGN/METHODS: Chronic EAE was induced in C57BL/6 mice by s.c. immunization with MOG40-55 emulsified in complete Freund's adjuvant. Pertussis Toxin was injected i.v. at days 0 and 2 post-immunization. Clinical score was daily measured based on tail/leg paralysis. TolBM-DCs were in vitro differenciated with GM-CSF in the presence of vitamin D3 (VD3) for 8 days. On day 7, maturation was induced with LPS. Viability, efficiency of differentiation and phenotype of tolBM-DCs were evaluated. To assess antigen specificity, tolBM-DCs were pulsed with MOG40-55, after the maturation stimulus (day 7) for 18h and cocultured with syngeneic splenocytes from mice with established EAE. RESULTS: TolBM-DCs displayed a semi-mature phenotype, exhibited by low levels of MHC class II and coestimulatory molecules (CD40, CD86) compared to control mature BM-DCs (mBM-DCs) differenciated in the absence of VD3. MOG40-55 loaded TolDCs showed to be poor stimulators of specific T cell proliferation of mice with EAE, compared to mBM-DCs. CONCLUSIONS: These results suggest that MOG-loaded TolDCs may be a powerful tool to induce specific T-cell hyporesponsiveness in EAE. Hence, treatment with tolDCs loaded with myelin peptides might be a potential therapy for EAE/MS. This model can be useful to establish parameters such as dose and route of administration prior to their translation to MS patients. Disclosure: Dr. Sellés-Moreno has nothing to disclose. Dr. Grau-López has nothing to disclose. Dr. Ramo Tello has nothing to disclose. Dr. Martínez-Cáceres has nothing to disclose.