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Regulation and function of class II major histocompatibility complex, CD40, and B7 expression in macrophages and microglia: Implications in neurological diseases

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Abstract

The ability of microglia, the brain’s resident macrophage, to present antigen through the class II major histocompatibility complex (MHC) to T cells allows these normally quiescent cells to play a critical role in shaping the outcome of many neurological diseases. The expression of class II MHC antigens and the costimulatory molecules CD40 and B7 on microglia and infiltrating macrophages is regulated through a complex network of cytokines in the inflamed brain. In this review, we describe the molecular mechanisms underlying class II MHC, CD40 and B7 regulation in microglia and macrophages. Our focus is on the cis-elements in the promoters of their genes and the transcription factors activated by cytokines that bind them. The functional implications of aberrant class II MHC, CD40 and B7 expression by microglia and macrophages as related to the diseases of Multiple Sclerosis and Alzheimer’s Disease are discussed.

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  1. Department of Cell Biology, University of Alabama at Birmingham, Room 395 MCLM, 35294-0005, Birmingham, Alabama, USA

    George M. O’Keefe, Vince T. Nguyen & Etty N. Benveniste

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  1. George M. O’Keefe
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  2. Vince T. Nguyen
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  3. Etty N. Benveniste
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Correspondence to Etty N. Benveniste.

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This work was supported in part by National Institutes of Health grants NS-36765, NS-39954, and MH-63650, and AmFAR grant 02797-RG (to ENB).

GMO and VNT were supported by National Institutes of Health Predoctoral Fellowships T32NS-07441 and T32AI-07493, respectively.

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O’Keefe, G.M., Nguyen, V.T. & Benveniste, E.N. Regulation and function of class II major histocompatibility complex, CD40, and B7 expression in macrophages and microglia: Implications in neurological diseases. Journal of NeuroVirology 8, 496–512 (2002). https://doi.org/10.1080/13550280290100941

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