Research: Dendritic Cells

Raϊch-Regué D, Grau-López L, Naranjo-Gómez M, Ramo-Tello C, Pujol-Borrell R, Martínez-Cáceres E, Borràs FE.Stable antigen-specific T-cell hyporesponsiveness induced by tolerogenic dendritic cells from multiple sclerosis patients. Eur J Immunol. 2012;42:771-82.


Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease of the central nervous system. Current therapies decrease the frequency of relapses and limit, to some extent, but do not prevent disease progression. Hence, new therapeutic approaches that modify the natural course of MS need to be identified. Tolerance induction to self-antigens using monocyte-derived dendritic cells (MDDCs) is a promising therapeutic strategy in autoimmunity. In this work, we sought to generate and characterize tolerogenic MDDCs (tolDCs) from relapsing-remitting (RR) MS patients, loaded with myelin peptides as specific antigen, with the aim of developing immunotherapeutics for MS. MDDCs were generated from both healthy-blood donors and RR-MS patients, and MDDC maturation was induced with a proinflammatory cytokine cocktail in the absence or presence of 1α,25-dihydroxyvitamin-D(3) , a tolerogenicity-inducing agent. tolDCs were generated from monocytes of RR-MS patients as efficiently as from monocytes of healthy subjects. The RR-M StolDCs expressed a stable semimature phenotype and an antiinflammatory profile as compared with untreated MDDCs. Importantly, myelin peptide-loaded tolDCs induced stable antigen-specific hyporesponsiveness in myelin-reactive T cells from RR-MS patients. These results suggest that myelin peptide-loaded tolDCs may be a powerful tool for inducing myelin-specific tolerance in RR-MS patient




However, recent experience with antigen-specific immune interventions in MS and some general caveats associated with cell-based-therapies highlight the challenges for clinical translation of the "immunologist's dream" of treating autoimmunity. 


This idea is to specifically block just the damaging immune response but leave the rest of the immune response untouched.

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