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Related Experiment Videos

Cellular immune response in multiple sclerosis plaques.

E A Boyle1, P L McGeer

  • 1Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver.

The American Journal of Pathology
|September 1, 1990
PubMed
Summary

In multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE), macrophages and microglia, not astrocytes, express class II major histocompatibility complex (MHC) antigens within plaques. These cells contain myelin debris, indicating their role in clearing damaged tissue.

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Area of Science:

  • Neuroimmunology
  • Pathology
  • Cell Biology

Background:

  • Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system.
  • The cellular and molecular mechanisms underlying plaque formation in MS are not fully understood.
  • Identifying the cell types responsible for antigen presentation in MS lesions is crucial for understanding disease pathogenesis.

Purpose of the Study:

  • To investigate the cell types expressing class II major histocompatibility complex (MHC) antigens in multiple sclerosis (MS) plaques.
  • To differentiate the roles of microglia/macrophages and astrocytes in antigen presentation within MS lesions.
  • To compare antigen-presenting cell populations in MS plaques with those in experimental allergic encephalomyelitis (EAE) in Lewis rats.

Main Methods:

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  • Immunohistochemical staining of MS plaques and EAE lesions.
  • Antibodies used included human leukocyte antigen (HLA)-DR, glial fibrillary acidic protein (GFAP), leukocyte common antigen (LCA), CD4, CD8, OX6, and OX17.
  • Counterstaining with oil red O to detect myelin debris.

Main Results:

  • Human leukocyte antigen (HLA)-DR-positive cells, primarily reactive microglia/macrophages, formed dense rings around MS plaques.
  • These cells contained significant amounts of myelin debris, as shown by oil red O staining.
  • Astrocytes, identified by GFAP staining, did not contain myelin debris and were distinct from HLA-DR-positive cells.
  • Similar Ia-positive (OX6, OX17) cells with reactive microglia/macrophage morphology and myelin debris were observed in EAE lesions.
  • Lymphocytes, including CD4 and CD8 positive T-cells, were found in perivascular cuffs and within the affected tissue.

Conclusions:

  • Macrophages and reactive microglia, rather than astrocytes, are the primary expressors of class II MHC antigens in active MS and EAE plaques.
  • These findings highlight the significant role of microglia/macrophages in myelin degradation and antigen presentation during demyelination.
  • The results provide insights into the cellular immune response within inflammatory lesions of the central nervous system.