Microglia in the immune surveillance of the brain: Human microglia constitutively express HLA-DR molecules

doi:10.1016/0165-5728(93)90191-Z

Journal of Neuroimmunology

Volume 48, Issue 2, November–December 1993, Pages 189-198

https://doi.org/10.1016/0165-5728(93)90191-Z Get rights and content

Abstract

The degree of MHC class II expression in histologically normal human brain biopsy or autopsy tissue is still controversial. According to the generally held view MHC class II expression is rather low in the normal brain with the exception of the white matter. In the present study, HLA-DR expression was examined immunocytochemically in different brain areas obtained from three autopsy cases with short post-mortem times (i.e. 6 h). Based on standard histological evaluation, the brain areas studied appeared as histologically normal tissue. In all brain areas there was a strong constitutive HLA-DR expression on ramified microglia. The number of HLA-DR-immunoreactive microglia was strongest in the white matter (the corpus callosum and the capsula interna for example). The border zone between white matter and grey matter, however, revealed a sharp contrast between a high density of HLA-DR-immunoreactive microglia in the white matter and a rather low number in the grey matter. In the grey matter, HLA-DR-immunoreactive microglia were much less frequent than in the white matter and more pronounced on perivascular cells. The staining and distribution pattern of HLA-DR-immunoreactive microglia was confirmed by immunocytochemistry with a panel of different anti-HLA-DR monoclonal antibodies as well as by quantitative analysis of the immunostaining. Unlike the HLA-DR immunoreactivity, HLA-ABC immunoreactivity (detecting MHC class I antigens) was confined to endothelia and not observed on microglia. In the choroid plexus stromal macrophages expressed both class I and II antigens (i.e. at a location which could provide the peripheral immune system access to CNS antigens). Constitutive HLA-DR expression by microglia qualifies them as the main resident antigen-presenting cell of the brain. The pronounced overall HLA-DR expression by resting microglia questions a central dogma of the brain as an immune-privileged site and further points to the key role of the microglia in brain immune surveillance.

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¹: Present address: Institute of Neuropathology, University Hospital, CH-8091 Zürich, Switzerland.

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Microglia in the immune surveillance of the brain: Human microglia constitutively express HLA-DR molecules

Abstract

J. Neuroimmunol.

J. Neuroimmunol.

J. Neurol. Sci.

Trends Neurosci.

Cytotoxicity of microglia

Glia

A subpopulation of bone marrow-derived macrophage-like cells shares a unique ion channel pattern with microglia

J. Neurosci. Res.

Biology of disease. Microglia in human disease, with an emphasis on the acquired immune deficiency syndrome

Lab. Invest.

Antigen presentation and tumor cytotoxicity by interferon-gamma treated microglial cells

Eur. J. Immunol.

Characterisation of two new monoclonal antibodies directed against rat microglia

J. Comp. Neurol.

Spinal cord microglial cells and DRG satellite cells rapidly respond to transection of the rat sciatic nerve

Restor. Neurol. Neurosci.

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J. Cereb. Blood Flow Metab.

Spinal cord microglia in experimental allergic neuritis: evidence for fast and remote activation

Lab. Invest.

Microglial involvement in experimental autoimmune inflammation of the peripheral and central nervous system

Glia

Toward an immunological definition of the blood-brain barrier: Significance of MHC class II positive perivascular cells

Ultrastructural location of major histocompatibility complex (MHC) class II positive perivascular cells in histologically normal brain tissue

J. Neuropathol. Exp. Neurol.

Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo

Science

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J. Neurosci. Res.

Neurological Autoimmune Disease and the trimolecular complex of T-lymphocytes

Annal. Neurol.