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Human microglia activate lymphoproliferative responses to recall viral antigens
S Dhib-Jalbut1, N Gogate, H Jiang
1Department of Neurology, University of Maryland School of Medicine, Baltimore 21201, USA.
Abstract:
The capacity of adult human microglia to activate memory T-lymphocyte responses to recall viral antigens in autologous peripheral blood lymphocytes (PBL) was examined using measles and influenza viruses. Microglia and peripheral blood macrophages were isolated form 6 patients who underwent surgical brain biopsies. Microglial cultures readily expressed high levels of HLA class II molecules under basal culture conditions. However, compared to macrophages, microglia appeared to express much lower levels of CD45, a phenotype that has been associated with the ability of rat brain macrophage/microglia to present antigen. PBL were depleted of macrophages (D-PBL) and the efficacy of the depletion was assessed by a reduction in the T-cell response to concanavalin A. D-PBL were reconstituted with macrophages, microglia, or in some cases microglia pretreated with interferon-gamma (IFN gamma). It was observed that microglia were as efficient as macrophages in presenting viral antigens. Pretreatment of microglia with IFN gamma did not enhance further antigen presentation. Oligodendrocytes which lack constitutive or inducible HLA class II molecules failed to present viral antigens. The results have implications of the direct function of microglia as perpetuators and possibly initiators of immune responses to virus infection in the central nervous system compartment.
Insights
Adult human microglia can activate memory T-lymphocytes to viral antigens, similar to macrophages. This suggests microglia play a key role in initiating and sustaining immune responses within the central nervous system during viral infections.
Area of Science:
- Neuroimmunology
- Cellular Immunology
- Virology
Background:
- Adult human microglia, the resident immune cells of the brain, are increasingly recognized for their roles beyond immune surveillance.
- Understanding their antigen-presenting capacity is crucial for deciphering immune responses within the central nervous system (CNS).
Purpose of the Study:
- To investigate the ability of adult human microglia to present viral antigens and activate memory T-lymphocytes.
- To compare the antigen-presenting efficacy of microglia with that of peripheral blood macrophages.
Main Methods:
- Isolation of microglia and macrophages from human brain biopsies.
- Assessment of HLA class II and CD45 expression on microglia and macrophages.
- T-lymphocyte activation assays using viral antigens (measles and influenza) with reconstituted peripheral blood lymphocytes (PBL).
Main Results:
- Microglia expressed high levels of HLA class II molecules, crucial for antigen presentation.
- Microglia demonstrated an antigen-presenting capacity comparable to macrophages in activating T-lymphocytes.
- Interferon-gamma (IFN-γ) pretreatment did not enhance microglial antigen presentation.
- Oligodendrocytes, lacking HLA class II, failed to present antigens.
Conclusions:
- Adult human microglia possess a significant capacity for antigen presentation, effectively activating memory T-lymphocytes.
- These findings highlight the potential of microglia to initiate and perpetuate immune responses against viral infections within the CNS.