title: Multiple sclerosis: distribution of inflammatory cells in newly forming lesions.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Clinical Neuroscience, Department of Medicine, University of Sydney, Sydney, Australia.
authors.forename: Andrew P D
authors.initials: AP
authors.lastname: Henderson
authors.forename: Michael H
authors.initials: MH
authors.lastname: Barnett
authors.forename: John D E
authors.initials: JD
authors.lastname: Parratt
authors.forename: John W
authors.initials: JW
authors.lastname: Prineas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D040502:Calgranulin B / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D003713:Dendritic Cells / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D009186:Myelin Sheath / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology*; D037121:Plant Lectins / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D040502:Calgranulin B; D037121:Plant Lectins; C017707:Ricinus communis agglutinin-1