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Efficiently stimulated adult microglia cross-prime naive CD8+ T cells injected in the brain
Ulrich Jarry1, Pascale Jeannin, Laurent Pineau
1L'UNAM Université, Université d'Angers, Angers, France.
Abstract:
Microglia are the major myeloid-immune cells of the brain parenchyma. In a steady state, microglia monitor their environment for pathogens or damaged cells. In response to neural injury or inflammation, microglia become competent APCs able to prime CD4(+) and CD8(+) T lymphocytes. We previously demonstrated that neonatal and adult microglia cross-present exogenous soluble Ags in vitro. However, whether microglia are able to cross-present Ag to naive CD8(+) T cells in vivo, within the brain microenvironment, remains undetermined. Here, we have designed an original protocol in order to exclude the involvement in cross-presentation activity of peripheral migrating APCs and of CNS-associated APCs. In C57Bl/6 mice, in which the body but not the head has been properly irradiated, we analyzed the ability of resident microglia to stimulate intracerebrally injected CD8(+) T cells in vivo. This study demonstrates for the first time that adult microglia cross-present Ag to naive CD8(+) T cells in vivo and that full microglia activation is required to overcome the inhibitory constrains of the brain and to render microglia able to cross-prime naive CD8(+) T cells injected in the brain. These observations offer new insights in brain-tumor immunotherapy based on the induction of cytotoxic antitumoral T cells.
Insights
Adult microglia can present antigens to T cells in the brain, a process crucial for immune responses. This finding advances understanding of brain immunity and potential cancer immunotherapies.
Area of Science:
- Neuroimmunology
- Cellular Immunology
Background:
- Microglia are the primary immune cells in the brain parenchyma.
- Activated microglia can act as antigen-presenting cells (APCs) for T lymphocytes.
- Previous studies showed in vitro cross-presentation by microglia, but in vivo evidence was lacking.
Purpose of the Study:
- To determine if adult microglia can cross-present antigens to naive CD8(+) T cells in vivo within the brain.
- To investigate the role of microglia activation in T cell priming in the central nervous system.
Main Methods:
- Developed a novel irradiation protocol in C57Bl/6 mice to isolate microglia's cross-presentation activity.
- Excluded peripheral and CNS-associated APCs by irradiating the body but not the head.
- Analyzed resident microglia's ability to stimulate intracerebrally injected CD8(+) T cells.
Main Results:
- Demonstrated for the first time that adult microglia cross-present antigens to naive CD8(+) T cells in vivo.
- Showed that full microglia activation is necessary to overcome brain's inhibitory constraints.
- Confirmed microglia's capacity to cross-prime T cells within the brain microenvironment.
Conclusions:
- Adult microglia possess the capability for in vivo cross-presentation of antigens to naive CD8(+) T cells.
- Effective microglia activation is essential for initiating T cell responses in the brain.
- These findings provide new perspectives for brain-tumor immunotherapy strategies targeting cytotoxic T cells.
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