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Regular Articles |
From the Laboratory of Organ and System
Pathophysiology,*
Istituto Superiore di Sanità, Rome;
and the Laboratory of Pathophysiology,
Centro
Ricerca Sperimentale, Istituto Regina Elena, Rome, Italy
Dendritic cells (DCs) are thought to be key elements in the
initiation and maintenance of autoimmune diseases. In this
study, we sought evidence that DCs recruited to the central
nervous system (CNS), a site that is primarily devoid of
resident DCs, play a role in the effector phase and propagation
of the immune response in experimental autoimmune encephalomyelitis
(EAE). After immunization of SJL mice with proteolipid protein 139-151
peptide, process-bearing cells expressing the DC markers
DEC-205 and CD11c appeared early in the spinal cord. During
acute, chronic, and relapsing EAE,
DEC-205+ DCs expressing a lymphostimulatory phenotype
(including the mature DC marker MIDC-8, major
histocompatibility complex class II, CD40, and CD86
molecules) accumulated within the CNS inflammatory cell infiltrates.
More prominent infiltration of the spinal cord parenchyma by mature DCs
was observed in mice with relapsing disease. Macrophage inflammatory
protein 3
, a chemokine active on DCs and
lymphocytes, and its receptor CCR6 were up-regulated in the CNS
during EAE. These findings suggest that intracerebral recruitment and
maturation of DCs may be crucial in the local stimulation and
maintenance of autoreactive immune responses, and that
therapeutic strategies aimed at manipulating DC migration could be
useful in the treatment of CNS autoimmune disorders.
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