Abstract
The CD1 protein family present lipid antigens to the immune system. CD1d has been observed in the CNS of MS patients, yet no studies have quantitatively characterized this expression and related it to inflammatory demyelinative activity in MS plaques. In this study, we set out to localize and quantify the presence of CD1d expression by astrocytes in MS brain tissue lesions. Formalin‐fixed, paraffin‐embedded MS and control brain tissues were examined. Lesions were classified as active, chronic active or chronic silent. Using immunofluorescence, the density of CD1d‐positive cells was determined in active lesions, chronic active lesion edges and chronic active lesion centers. The percentage of CD1d‐positive cells that were GFAP‐positive was also determined in each of these regions. CD1d immunoreactivity was significantly increased in MS compared to control tissue, was significantly more prevalent in areas of active demyelination, and colocalized with GFAP‐positive reactive astrocytes. Increases of CD1d immunoreactivity in the CNS of MS patients being greatest in areas of active demyelination and localized to GFAP‐positive astrocytes lend support to the hypothesis of a lipid‐targeted autoimmune process contributing to the pathogenesis of MS.
Highlights
The pathological hallmarks of multiple sclerosis (MS) plaques are inflammation, demyelination and gliosis; remyelination and axonal loss are recognized as important components of the lesion [17]
The area outlined by the extent of complete demyelination—as evidenced by lack of Sudan Black B (SBB) staining—was considered the lesion center, while as noted in the Materials and Methods, the lesion edge was defined as an area extending 500 μm out from the interface between myelinated and demyelinated white matter (Figure 1C)
The outlining based on SBB corresponded well with where demyelinated white matter abutted myelinated white matter as shown by Luxol fast blue (LFB) positivity; this area corresponded with the rim of increased HLA-DR positive cell staining which typically declined beyond this lesion edge (Figure 1B,C)
Summary
The pathological hallmarks of multiple sclerosis (MS) plaques are inflammation, demyelination and gliosis; remyelination and axonal loss are recognized as important components of the lesion [17]. MS has long been thought to be an autoimmune disorder directed against some as yet undetermined epitope in the central nervous system (CNS), the myelin sheath [16, 25]. Very little attention has been directed to lipid autoimmunity in the pathogenesis of MS. An increase in the expression of CD1b was found in MS lesions, which was restricted primarily to areas of active demyelination, with minimal reactivity found elsewhere, and in control white matter [4]. CD1b was expressed primarily in hypertrophic astrocytes and could be seen in perivascular inflammatory cells both within the lesion and surrounding it. In lesions from a single case of acute MS, CD1d was localized to reactive astrocytes and occasional microglia [9]
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