Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adult
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Aged
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Astrocytes / chemistry
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Astrocytes / immunology
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CD4-Positive T-Lymphocytes / chemistry
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / chemistry
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CD8-Positive T-Lymphocytes / immunology
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Central Nervous System / chemistry*
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Central Nervous System / immunology*
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Central Nervous System / pathology
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Cerebrospinal Fluid / cytology
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Chemokine CXCL10
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Chemokines, CXC / analysis*
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Female
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Flow Cytometry
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Humans
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Male
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Middle Aged
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Multiple Sclerosis / immunology*
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Multiple Sclerosis / pathology
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Myelitis, Transverse / immunology
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Myelitis, Transverse / pathology
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Optic Neuritis / immunology
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Optic Neuritis / pathology
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Receptors, CXCR3
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Receptors, Chemokine / analysis*
Substances
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CXCR3 protein, human
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Chemokine CXCL10
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Chemokines, CXC
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Receptors, CXCR3
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Receptors, Chemokine