Related Experiment Videos
Microglia in the immune surveillance of the brain: human microglia constitutively express HLA-DR molecules
J Gehrmann1, R B Banati, G W Kreutzberg
1Max-Planck-Institute of Psychiatry, Department of Neuromorphology, Martinsried near Munich, Germany.
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.
Insights
Resting microglia in normal human brain tissue show strong HLA-DR expression, particularly in white matter. This finding challenges the concept of brain immune privilege and highlights microglia
Area of Science:
- Neuroimmunology
- Human Brain Tissue Analysis
- Immunohistochemistry
Background:
- MHC class II expression in normal human brain tissue is debated, with some views suggesting low levels except in white matter.
- Previous understanding posits the brain as an immune-privileged site, implying limited immune cell activity and antigen presentation.
Purpose of the Study:
- To investigate the constitutive expression of HLA-DR (MHC class II) in histologically normal human brain autopsy tissue.
- To compare HLA-DR expression patterns in different brain regions, focusing on microglia and other cell types.
- To evaluate the implications of observed HLA-DR expression on the concept of brain immune privilege.
Main Methods:
- Immunocytochemical examination of HLA-DR expression in brain areas from three autopsy cases with short post-mortem intervals (6 hours).
- Histological evaluation confirmed the normal appearance of all studied brain areas.
- Confirmation of staining patterns using multiple anti-HLA-DR monoclonal antibodies and quantitative analysis.
Main Results:
- Strong constitutive HLA-DR expression was observed on ramified microglia across all examined brain areas.
- Microglial HLA-DR expression was most abundant in white matter (e.g., corpus callosum, capsula interna) compared to grey matter.
- A sharp contrast in microglial HLA-DR density was noted at the white-grey matter border; HLA-ABC (MHC class I) was found on endothelia, not microglia.
Conclusions:
- Constitutive HLA-DR expression by microglia identifies them as the primary resident antigen-presenting cells in the human brain.
- The widespread and strong HLA-DR expression by resting microglia challenges the traditional view of the brain as an immune-privileged site.
- Microglia play a crucial role in brain immune surveillance, evidenced by their antigen-presenting capabilities.