Monocytes in active multiple sclerosis: intact regulation of HLA-DR density in vitro despite decreased HLA-DR density in vivo |
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Authors: | Richard M. Ransohoff Vincent K. Tuohy Barbara P. Barna Richard A. Rudick |
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Affiliation: | Department of Molecular Biology, Cleveland Clinic Foundation, OH. |
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Abstract: | HLA-DR expression on circulating monocytes varies as a function of disease activity in patients with multiple sclerosis (MS), a putative immunopathological demyelinating disorder. Specifically, monocytes isolated from subjects with active MS exhibit reduced HLA-DR antigen density, and immunoregulatory aberrations such as impaired T lymphocyte-mediated suppression correlate strongly with this quantitative defect. To address the mechanism underlying this phenomenon, we compared in vitro regulation of HLA-DR by interferon beta (IFN beta), interferon gamma (IFN gamma), and lipopolysaccharide (LPS) in monocytes from patients with stable and active MS and normal individuals. Interferon-gamma and LPS enhanced monocyte expression of HLA-DR equally in both MS patient groups, suggesting that underexpression of HLA-DR in active MS was not explained by impaired in vivo monocyte responsiveness. Furthermore, interferon regulation of HLA-DR in normals and stable MS subjects was indistinguishable, indicating that aberrant interferon-mediated regulation of class II major histocompatibility complex (MHC) on circulating monocytes does not appear to be a characteristic of the MS disease state. |
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Keywords: | Multiple sclerosis Class II major histocompatibility complex Monocyte Interferon |
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