Upregulation of transcription factors controlling MHC expression in multiple sclerosis lesions

The expression of major histocompatibility complex (MHC) class I and class II in the CNS has received considerable interest because of its importance in neurodegenerative or inflammatory diseases, such as multiple sclerosis ( MS). However, at the moment nothing is known about the expression patterns of transcription factors controlling MHC expression in MS lesions. Here, we performed an extensive immunohistochemical analysis on MS affected postmor tem brain tissue to determine the cellular localization and distribution of different MHC-controlling transcription factors. We show that phagocytic m acrophages in active demyelinating MS lesions displayed a moderate to stron g immunostaining of the MHC-specific transcription factors RFX and CIITA, a s well as the general transcription factors NF-kappaB, IRF1, STAT1, USF, an d CREB, which was congruent with a strongly enhanced expression of HLA-DR, HIA-DQ, HLA-DP, and HLA class I. In the normal-appearing white matter (NAWM ), clusters of activated microglial cells forming preactive lesions display ed an overall stronger expression level of these transcription factors, com bined with a strong to intense level of MHC class I and class II immunostai ning. In general, astrocytes and oligodendrocytes either did not express, o r weakly expressed, these transcription factors, correlating with a lack of MHC class II and weak MHC class I expression. Together, the elevated expre ssion level of transcription factors governing expression of MHC class I an d class II molecules in activated microglial cells and phagocytic macrophag es strongly suggests a general state of microglial cell activation in MS le sions. (C) 2001 Wiley-Liss, Inc.