UBC Theses and Dissertations
Characterization of the presence and distribution of CD1d in the central nervous system of multiple sclerosis Muir, Fraser
Background: Research into diffusely abnormal white matter (DAWM) in archival MS brain tissue has shown that there is a lipid-specific depletion with preservation of myelin proteins within DAWM, implicating a response against myelin lipids in multiple sclerosis (MS). CD1, the Class I MHC-like protein family, present lipid antigens to the immune system. CD1a, b, and d have been observed in the central nervous system (CNS) of MS patients, yet no studies have quantified the presence of CD1d in the CNS. Methods: Archival formalin-fixed, paraffin-embedded MS and control brain tissues were sectioned and stained with luxol fast blue (LFB) for myelin, and HLA-DR (class II MHC). Lesions were categorized as active, or chronic active, based upon HLA-DR and LFB staining characteristics. Sections were stained for CD1d, ionized calcium-binding adapter molecule 1 (Iba-1, microglia), glial fibrillary acidic protein (GFAP, astrocytes), DAPI (nuclei), and Sudan Black B (myelin). Tissues were imaged using an epifluorescent microscope and lesions were outlined based on absence of myelin staining. CD1d-positive cells were quantified per mm² and the number of cells double labeling with Iba-1 or GFAP were noted. Results: CD1d immunoreactivity was significantly increased in MS compared to control tissue. CD1d-positive cells were more prevalent in areas of active demyelination in MS lesions, and colocalized primarily with GFAP-positive reactive astrocytes. The edges of lesions contained CD1d-positive cells in similar numbers to active lesions but had significantly more than quiescent lesion centers. CD1d was found occasionally within Iba-1-positive cells. Conclusions: Our findings show increased CD1d in the CNS of MS patients, and demonstrate positivity being greatest in areas of active demyelination which is novel and supports a lipid-targeted autoimmune process contributing to the pathogenesis of MS. CD1d is primarily localized to GFAP-positive astrocytes and highlights a role for these cells compared to the rare CD1d-positive microglia.
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