Upregulation of transcription factors controlling MHC expression in multiple sclerosis lesions

Authors

  • Sam J.P. Gobin,

    Corresponding author
    1. Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    • Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
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  • Lisette Montagne,

    1. Department of Pathology, Division of Neuropathology, Institute of Neurosciences, Vrije Universiteit Medical Center, Amsterdam, The Netherlands
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  • Marlijn Van Zutphen,

    1. Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
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  • Paul Van Der Valk,

    1. Department of Pathology, Division of Neuropathology, Institute of Neurosciences, Vrije Universiteit Medical Center, Amsterdam, The Netherlands
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  • Peter J. Van Den Elsen,

    1. Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
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  • Corline J.A. De Groot

    1. Department of Pathology, Division of Neuropathology, Institute of Neurosciences, Vrije Universiteit Medical Center, Amsterdam, The Netherlands
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Abstract

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 postmortem brain tissue to determine the cellular localization and distribution of different MHC-controlling transcription factors. We show that phagocytic macrophages in active demyelinating MS lesions displayed a moderate to strong immunostaining of the MHC-specific transcription factors RFX and CIITA, as well as the general transcription factors NF-κB, IRF1, STAT1, USF, and CREB, which was congruent with a strongly enhanced expression of HLA-DR, HLA-DQ, HLA-DP, and HLA class I. In the normal-appearing white matter (NAWM), clusters of activated microglial cells forming preactive lesions displayed an overall stronger expression level of these transcription factors, combined with a strong to intense level of MHC class I and class II immunostaining. In general, astrocytes and oligodendrocytes either did not express, or weakly expressed, these transcription factors, correlating with a lack of MHC class II and weak MHC class I expression. Together, the elevated expression level of transcription factors governing expression of MHC class I and class II molecules in activated microglial cells and phagocytic macrophages strongly suggests a general state of microglial cell activation in MS lesions. GLIA 36:68–77, 2001. © 2001 Wiley-Liss, Inc.

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