EXPRESSION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I ANTIGENS IN THE DEMYELINATING TWITCHER CNS AND PNS

The expression of the major histocompatibility complex Class I antigen s (Class I) was investigated in the nervous system of twitcher (C57BL/ 6J-twi), a murine model of Krabbe disease in humans. Class I mRNA expr ession was low in wild type and in twitcher mice prior to the onset of demyelination, However, immunoreactivity for Class I antigens was dem onstrated in the spindle-shaped cells in the sciatic nerve and in rami fied microglia, endothelial cells and Bergmann glia. In twitcher, tran scription of Class I mRNA increased significantly with the progression of demyelination and Mac-1(+) macrophages/microglia express Class I i mmunoreactivity, Class I immunoreactivity was also found in CD3(+) T-c ells that were scattered in demyelinating lesions, CD8(+) or CD4(+) ce lls were also found in the demyelinating area, The results of this stu dy indicate that immunoreactivity to Class I antigens is detected in c ertain cells even in the wild-type mice and that Class I expression is enhanced in the twitcher nervous system paralleling the progression o f demyelination, Expression of MHC molecules in nonimmunological demye linating disease such as twitcher may suggest a role of Class I molecu les in the progression of demyelination, Alternatively, the expression may be a non-specific cellular response to the breakdown of myelin. ( C) 1997 Wiley-Liss, Inc.