Dendritic cells are abundant in non-lesional gray matter in multiple sclerosis.
We have analyzed the localization of dendritic cells (DCs) in non-lesional gray matter (NLGM) in comparison to non-lesional white matter (NLWM) and acute or chronic active multiple sclerosis (MS) lesions. Immunohistochemistry was performed on cryostat sections for DCs markers (CD209, CD205, CD83) and other markers for inflammatory cells (CD68, CD8, CD4, CD3, CCR7, CCR5). We found cells expressing CD209 and containing myelin basic protein in both perivascular and parenchymal areas of NLGM. Our findings showing the expression of CD209(+) cells in NLGM parenchymal areas are surprising relative to the previous literature which reported the presence of CD209(+) DCs only in MS plaque perivascular areas. Although less numerous than CD209(+) cells, NLGM cells expressing mature DCs marker CD205 were consistently detected in perivascular cuffs of most lesions. In double labeling experiments, some but not all of the CD209(+) cells also expressed CD68 and CCR5. We also found CD209(+) cells in close contact with CD3(+) lymphocytes suggesting that DCs might contribute to the local activation of pathogenic T cells in the NLGM. Since injury to the NLGM is one of the key factors associated with disability accumulation, targeting DCs may represent a possible new therapeutic approach in MS to prevent disease progression.
Cudrici
Cornelia
C
Department of Neurology, University of Maryland, Baltimore, MD 21201, USA.
Ito
Takahiro
T
Zafranskaia
Ekaterina
E
Niculescu
Florin
F
Mullen
Katherine M
KM
Vlaicu
Sonia
S
Judge
Susan I V
SI
Calabresi
Peter A
PA
Rus
Horea
H
D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001344:Autopsy; D001921:Brain / Q000473:pathology*; D017252:CD3 Complex / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology*; D010487:Periaqueductal Gray / Q000276:immunology / Q000473:pathology*; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000032:analysis; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; C515370:CCR7 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule