Multiple sclerosis: a study of CXCL10 and CXCR3 co-localization in the inflamed central nervous system.
T-cell accumulation in the central nervous system (CNS) is considered crucial to the pathogenesis of multiple sclerosis (MS). We found that the majority of T cells within the cerebrospinal fluid (CSF) compartment expressed the CXC chemokine receptor 3 (CXCR), independent of CNS inflammation. Quantitative immunohistochemistry revealed continuous accumulation of CXCR3+ T cells during MS lesion formation. The expression of one CXCR3 ligand, interferon (IFN)-gamma-inducible protein of 10 kDa (IP-10)/CXC chemokine ligand (CXCL) 10 was elevated in MS CSF, spatially associated with demyelination in CNS tissue sections and correlated tightly with CXCR3 expression. These data suggest a critical role for CXCL10 and CXCR3 in the accumulation of T cells in the CNS of MS patients.
Sørensen
Torben L
TL
The MS Clinic, Department of Neurology, University of Copenhagen, Glostrup Hospital, 2600 Glostrup, Denmark. torbenls@dadlnet.dk
Trebst
Corinna
C
Kivisäkk
Pia
P
Klaege
Karen L
KL
Majmudar
Amit
A
Ravid
Rivka
R
Lassmann
Hans
H
Olsen
David B
DB
Strieter
Robert M
RM
Ransohoff
Richard M
RM
Sellebjerg
Finn
F
D000328:Adult; D000368:Aged; D001253:Astrocytes / Q000737:chemistry / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D002490:Central Nervous System / Q000737:chemistry* / Q000276:immunology* / Q000473:pathology; D002555:Cerebrospinal Fluid / Q000166:cytology; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000032:analysis*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology; D009188:Myelitis, Transverse / Q000276:immunology / Q000473:pathology; D009902:Optic Neuritis / Q000276:immunology / Q000473:pathology; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000032:analysis*
C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine