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MHC II expression in the CNS after long-term demyelination
B Cannella1, D A Aquino, C S Raine
1Department of Pathology (Neuropathology), Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Journal of Neuropathology and Experimental Neurology
|July 1, 1995
Summary
Chronic demyelination does not prevent central nervous system (CNS) tissue from expressing major histocompatibility complex (MHC) class II molecules. This suggests potential for CD4+ T cell interaction in chronic multiple sclerosis lesions.
Area of Science:
- Neuroimmunology
- Cellular Biology
Background:
- Chronic demyelination in the central nervous system (CNS) is a hallmark of diseases like multiple sclerosis.
- The capacity of demyelinated CNS tissue to modulate immune responses, particularly through major histocompatibility complex (MHC) class II expression, remains incompletely understood.
- Previous research indicated that 3-week in vitro demyelination prevents remyelination.
Purpose of the Study:
- To investigate the expression of MHC class II molecules in chronically demyelinated mouse spinal cord cultures.
- To determine if interferon gamma (IFN gamma) can upregulate MHC class II expression in these cultures.
- To assess the implications for CD4+ T cell interaction in chronic demyelinating lesions.
Main Methods:
- Mouse spinal cord cultures were exposed to demyelinating anti-white matter (WM) serum for 1 and 3 weeks.
- Major histocompatibility complex (MHC) class II expression was analyzed using immunocytochemistry, Western blotting, and Northern blotting.
- Cultures were treated with or without interferon gamma (IFN gamma) to assess upregulation.
Main Results:
- Cultures retained the ability to express MHC class II molecules after 1 and 3 weeks of demyelination.
- Interferon gamma (IFN gamma) significantly upregulated MHC class II expression in both control and demyelinated cultures.
- MHC class II expression was observed on astrocytes and was slightly higher in anti-WM-treated cultures compared to controls.
- Western and Northern blots confirmed increased MHC class II expression and mRNA levels, with no significant differences between anti-WM and complement-treated groups after IFN gamma exposure.
Conclusions:
- Long-term demyelinated CNS tissue retains the capacity for major histocompatibility complex (MHC) class II expression.
- This sustained expression suggests that chronically demyelinated CNS tissue can potentially interact with CD4+ T cells.
- These findings are significant for understanding the immunopathology and progression of chronic multiple sclerosis lesions.