title: 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.
authors.affiliation: L'UNAM Université, Université d'Angers, Angers, France.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Jarry
authors.forename: Pascale
authors.initials: P
authors.lastname: Jeannin
authors.forename: Laurent
authors.initials: L
authors.lastname: Pineau
authors.forename: Sabrina
authors.initials: S
authors.lastname: Donnou
authors.forename: Yves
authors.initials: Y
authors.lastname: Delneste
authors.forename: Dominique
authors.initials: D
authors.lastname: Couez
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D000941:Antigens / Q000276:immunology; D001921:Brain / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D045142:Cross-Priming; D005720:Gamma Rays; D007276:Injections, Intraventricular; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000276:immunology*; D012995:Solubility
chemical_list: D000941:Antigens