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Multiple sclerosis: Distribution of inflammatory cells in newly forming lesions
Author(s) -
Henderson Andrew P. D.,
Barnett Michael H.,
Parratt John D. E.,
Prineas John W.
Publication year - 2009
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21800
Subject(s) - myelin , microglia , multiple sclerosis , oligodendrocyte , biology , macrophage , immune system , pathology , immunology , t cell , inflammation , microbiology and biotechnology , medicine , central nervous system , neuroscience , in vitro , biochemistry
Objective CD4 T‐cell–dependent macrophage activation directed against a myelin or oligodendrocyte antigen is generally thought to be the mechanism causing myelin destruction in multiple sclerosis (MS). However, areas within expanding MS lesions may exhibit prominent oligodendrocyte loss and apoptosis in the absence of infiltrating lymphocytes. The present study was designed to further investigate the inflammatory profile of different regions within rapidly expanding MS lesions. Methods Twenty‐six active lesions from 11 patients with early MS were serially sectioned and immunostained for T and B cells, plasma cells, ramified microglia, macrophages, monocytes, and CD209‐positive dendritic cells. Cell counts were compared in prephagocytic, phagocytic, and immediately postphagocytic areas. Results Parenchymal T and B cells were largely absent in areas of initial oligodendrocyte loss and in areas of degenerate and dead myelin infiltrated by myelin phagocytes. In contrast, trailing areas of complete demyelination packed with lipid macrophages, and, in some lesions, regenerating oligodendrocytes, showed large numbers of T cells, B cells, and immunoglobulin G (IgG)‐positive plasma cells. Lesions in 2 exceptionally early cases contained relatively few T and B cells, and no IgG‐positive plasma cells. Interpretation Early loss of oligodendrocytes is a prominent feature in tissue bordering rapidly expanding MS lesions. Macrophage activity is largely an innate scavenging response to the presence of degenerate and dead myelin. Adaptive immune activity involving T and B cells is conspicuous chiefly in recently demyelinated tissue, which may show signs of oligodendrocyte regeneration. The findings suggest that plaque formation has some basis other than destructive cell‐mediated immunity directed against a myelin or oligodendrocyte antigen. Ann Neurol 2009;66:739–753