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Efficiently stimulated adult microglia cross-prime naive CD8+T cells injected in the brain

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.

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https://hal.univ-angers.fr/hal-03389740
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Soumis le : jeudi 21 octobre 2021 - 10:22:30
Dernière modification le : mercredi 10 novembre 2021 - 15:32:04

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Ulrich Jarry, Pascale Jeannin, Laurent Pineau, Sabrina Donnou, Yves Delneste, et al.. Efficiently stimulated adult microglia cross-prime naive CD8+T cells injected in the brain. European Journal of Immunology, 2013, 43 (5), pp.1173 - 1184. ⟨10.1002/eji.201243040⟩. ⟨hal-03389740⟩

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