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CD83-positive dendritic cells are present in occasional perivascular cuffs in multiple sclerosis lesions
J Plumb1, M A Armstrong, M Duddy
1Neuropathology Laboratory, Royal Group of Hospitals Trust, Belfast, Northern Ireland, UK.
Insights
Dendritic cells (DCs) are implicated in multiple sclerosis (MS) pathogenesis. Researchers found mature DCs (CD83-positive cells) in MS lesions, suggesting peripheral origins and migration to the CNS.
Area of Science:
- Neuroimmunology
- Dendritic Cell Biology
Background:
- Multiple sclerosis (MS) involves central nervous system (CNS) damage mediated by T cells.
- Dendritic cells (DCs) are crucial antigen-presenting cells influencing T-cell responses.
Purpose of the Study:
- To investigate the presence and distribution of immature (CD1a+) and mature (CD83+) dendritic cells in multiple sclerosis CNS tissue.
- To explore the potential origin and migration patterns of DCs in MS lesions.
Main Methods:
- Immunocytochemistry was used to analyze tissue sections from 12 MS cases and controls.
- Monoclonal antibodies targeting CD1a (immature DC) and CD83 (mature DC) were employed.
- Tissues examined included recent demyelinating lesions, chronic plaques, and normal-appearing white matter (NAWM).
Main Results:
- No CD1a-positive cells were detected in MS or control CNS tissues.
- CD83-positive cells were absent in control tissues and most MS perivascular cuffs.
- Small numbers of CD83-positive cells were found in occasional perivascular cuffs in recent MS lesions, chronic plaques, and NAWM.
- CD83-positive cells were detected in the parenchyma of one MS NAWM area with intense immunological activity.
Conclusions:
- Mature dendritic cells are present in active and inactive MS lesions, as well as normal-appearing white matter.
- These findings suggest that DCs in MS lesions may originate from peripheral monocytes or immature DCs.
- DCs likely migrate to the CNS in response to chemokines, contributing to MS immunopathology.
Abstract:
Multiple sclerosis (MS) has a wide spectrum of clinical courses, characterized by multifocal central nervous system (CNS) damage, postulated to be mediated by CNS antigen-specific T cells. Dendritic cells (DC), the most potent antigen-presenting cell, play a pivotal role in the decision between T-cell activation or anergy. Monoclonal antibodies to CD1a (immature DC) and CD83 (mature DC) were used to screen lesions with evidence of recent demyelinating activity and chronic plaque and normal appearing white matter (NAWM) tissue sections from 12 MS cases by immunocytochemistry. No CD1a-positive cells were detected in the MS or control CNS tissue blocks investigated. CD83-positive cells were not detected in tissues from any of the control cases or in the majority of perivascular cuffs in the MS tissue sections. However; in eight of the MS tissue blocks with evidence of recent demyelination, and in one block each from chronic plaque and NAWM, small numbers of distinct CD83-positive cells were present within occasional perivascular cuffs. In one area only of MS NAWM were CD83-positive cells detected in the tissue parenchyma, in an area of intense immunological activity. DC in MS tissue may originate in the peripheral circulation as monocytes or immature DC and migrate to areas of plaque in response to signals received from CNS-produced chemokines.
