Research: Dendritic Cells


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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