Potential conflict of interest: Nothing to report.
Multiple sclerosis: Distribution of inflammatory cells in newly forming lesions†
Article first published online: 13 JUL 2009
Copyright © 2009 American Neurological Association
Annals of Neurology
Volume 66, Issue 6, pages 739–753, December 2009
How to Cite
Henderson, A. P. D., Barnett, M. H., Parratt, J. D. E. and Prineas, J. W. (2009), Multiple sclerosis: Distribution of inflammatory cells in newly forming lesions. Ann Neurol., 66: 739–753. doi: 10.1002/ana.21800
- Issue published online: 23 DEC 2009
- Article first published online: 13 JUL 2009
- Accepted manuscript online: 13 JUL 2009 12:00AM EST
- Manuscript Accepted: 1 JUL 2009
- Manuscript Revised: 26 JUN 2009
- Manuscript Received: 14 APR 2009
- Biogen Idec (Australia)
- MS Society of Great Britain and Northern Ireland
- NSW Ministry for Science and Medical Research
- National Multiple Sclerosis Society. Grant Number: RG 2731-A-B
- Multiple Sclerosis Research Australia
- National Health and Medical Research Council of Australia Scholarship
- Nerve Research Foundation
- University of Sydney
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.
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.
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.
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