Expression of major histocompatibility complex class I antigens in the demyelinating twitcher CNS and PNS.

ABSTRACT

The expression of the major histocompatibility complex Class I antigens (Class I) was investigated in the nervous system of twitcher (C57BL/6J-twi), a murine model of Krabbe disease in humans. Class I mRNA expression was low in wild type and in twitcher mice prior to the onset of demyelination. However, immunoreactivity for Class I antigens was demonstrated in the spindle-shaped cells in the sciatic nerve and in ramified microglia, endothelial cells and Bergmann glia. In twitcher, transcription of Class I mRNA increased significantly with the progression of demyelination and Mac-1+ macrophages/microglia express Class I immunoreactivity. Class I immunoreactivity was also found in CD3+ T-cells that were scattered in demyelinating lesions. CD8+ or CD4+ cells were also found in the demyelinating area. The results of this study indicate that immunoreactivity to Class I antigens is detected in certain cells even in the wild-type mice and that Class I expression is enhanced in the twitcher nervous system paralleling the progression of demyelination. Expression of MHC molecules in non-immunological demyelinating disease such as twitcher may suggest a role of Class I molecules in the progression of demyelination. Alternatively, the expression may be a non-specific cellular response to the breakdown of myelin.