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Bone marrow derived elements and resident microglia in brain inflammation
H Lassmann1, M Schmied, K Vass
1Research Unit for Experimental Neuropathology, Austrian Academy of Sciences, Vienna.
Insights
The central nervous system (CNS) has circulating T-lymphocytes and monocytes, with microglia acting as effector cells in brain inflammation models like experimental autoimmune encephalomyelitis (EAE). Resident microglia are stable, unlike meningeal and perivascular monocytes.
Area of Science:
- Neuroimmunology
- Cell Biology
- Virology
Background:
- Human immunodeficiency virus (HIV) central nervous system (CNS) infection relies on infected cell migration into the brain.
- Understanding hematogenous cell dynamics in the CNS is crucial for studying neuroinflammation and HIV pathogenesis.
Purpose of the Study:
- To investigate the homing and turnover of bone marrow-derived cells within the CNS.
- To analyze these dynamics under normal conditions and during experimental autoimmune encephalomyelitis (EAE), a model of brain inflammation.
Main Methods:
- Quantitative light and electron microscopic immunocytochemistry.
- Radiation bone marrow chimeras were used to track cell origins.
- Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats.
Main Results:
- The CNS is patrolled by T-lymphocytes and monocytes; meningeal and perivascular monocyte turnover accelerates during inflammation.
- Resident microglia form a stable cell pool, rarely replaced by hematogenous cells, even post-inflammation.
- In chimeric animals, microglia, astrocytes, and ependymal cells did not present antigens, yet EAE inflammatory responses were similar to controls.
- Resident microglia express the macrophage activation antigen ED1, indicating effector function.
Conclusions:
- Microglia function as effector cells in experimental autoimmune encephalomyelitis (EAE) lesions.
- Hematogenous cell turnover in the CNS differs significantly between monocytes and resident microglia.
- Resident microglia are a distinct and stable cell population within the adult CNS.
Abstract:
Infection of the central nervous (CNS) system by the human immunodeficiency virus (HIV) depends on the migration of infected hematogenous cells into the brain. We thus used quantitative light and electron microscopic immunocytochemistry to study the homing and turnover of bone marrow derived cells in the CNS in radiation bone marrow chimeras under normal conditions and in experimental autoimmune encephalomyelitis (EAE) as an experimental model of brain inflammation. Our studies suggest the following conclusions. First, the central nervous system is continuously patrolled by a small number of T-lymphocytes and monocytes. Meningeal and perivascular monocytes are slowly replaced by hematogenous cells under normal conditions, and this turnover is accelerated in the course of inflammation. In contrast, resident microglia represent a very stable cell pool, which in adult animals is only exceptionally replaced by hematogenous cells, even after recovery from severe brain inflammation. Second, although in bone-marrow-chimeric animals resident microglia, astrocytes, and ependymal cells are not able to present antigen to Lewis T-lymphocytes, the inflammatory reaction in EAE is qualitatively and quantitatively similar in these animals compared to fully histocompatible Lewis rats. Finally, resident microglia express the macrophage activation antigen ED1. Thus, microglia cells appear to function as effector cells in EAE lesions.