title: Dendritic cells in multiple sclerosis lesions: maturation stage, myelin uptake, and interaction with proliferating T cells.
abstract: In multiple sclerosis (MS), dendritic cells (DCs) recruited to the central nervous system (CNS) are thought to be involved in the regulation of autoimmune responses directed against myelin antigens. To better understand the role of DCs in CNS inflammation, we performed a detailed immunohistochemical analysis of DC maturation markers and of DC relationship to CNS-infiltrating T cells in autopsy brain tissue of patients with MS. We also investigated the presence of DCs containing myelin debris in MS lesions. Myeloid DC subsets were identified using the following markers: CD1a for immature DCs; DC-SIGN for immature and mature DCs; and fascin, CD83, DC-LAMP, and CCR7 for mature DCs. The most common finding was the presence of cells expressing DC-SIGN and containing myelin components in the perivascular cuffs of early active and chronic (both active and inactive) MS lesions. Perivascular CD1a DCs were detected in active lesions in only one of 10 patients with MS who were examined. Although less numerous than DC-SIGN DCs, cells expressing mature DC markers were consistently detected in the inflamed meninges and perivascular cuffs of most active lesions examined. CCR7 immunostaining was predominantly confined to activated microglia at the lesion edges. Some perivascular DC-SIGN cells were found in close proximity to or contacting rare proliferating lymphocytes, most of which expressed the DC-SIGN ligand ICAM-3 and CD8. These data suggest that DCs recruited and maturing in MS lesions, where self-antigens are made available by continuous myelin destruction, may contribute to the local activation and expansion of presumably pathogenic T cells.
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Serafini
authors.forename: Barbara
authors.initials: B
authors.lastname: Rosicarelli
authors.forename: Roberta
authors.initials: R
authors.lastname: Magliozzi
authors.forename: Egidio
authors.initials: E
authors.lastname: Stigliano
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Capello
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: Mancardi
authors.forename: Francesca
authors.initials: F
authors.lastname: Aloisi
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D016827:CD8 Antigens / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000502:physiology*; D005260:Female; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology; D009186:Myelin Sheath / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015703:Antigens, CD; D051940:B7-2 Antigen; D015415:Biomarkers; D016827:CD8 Antigens; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C497964:CD86 protein, human; C483616:ICAM3 protein, human