PMID- 23529826 OWN - NLM STAT- MEDLINE DCOM- 20130617 LR - 20131029 IS - 1521-4141 (Electronic) IS - 0014-2980 (Linking) VI - 43 IP - 5 DP - 2013 May TI - Efficiently stimulated adult microglia cross-prime naive CD8+ T cells injected in the brain. PG - 1173-84 LID - 10.1002/eji.201243040 [doi] AB - 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. CI - (c) 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Jarry, Ulrich AU - Jarry U AD - L'UNAM Universite, Universite d'Angers, Angers, France. FAU - Jeannin, Pascale AU - Jeannin P FAU - Pineau, Laurent AU - Pineau L FAU - Donnou, Sabrina AU - Donnou S FAU - Delneste, Yves AU - Delneste Y FAU - Couez, Dominique AU - Couez D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130409 PL - Germany TA - Eur J Immunol JT - European journal of immunology JID - 1273201 RN - 0 (Antigens) SB - IM MH - Animals MH - Antigen Presentation MH - Antigen-Presenting Cells/cytology/*immunology MH - Antigens/immunology MH - Brain/cytology/*immunology MH - CD8-Positive T-Lymphocytes/*immunology/transplantation MH - *Cross-Priming MH - Gamma Rays MH - Injections, Intraventricular MH - Mice MH - Mice, Inbred C57BL MH - Microglia/cytology/*immunology MH - Solubility EDAT- 2013/03/27 06:00 MHDA- 2013/06/19 06:00 CRDT- 2013/03/27 06:00 PHST- 2012/10/02 00:00 [received] PHST- 2013/01/31 00:00 [revised] PHST- 2013/02/21 00:00 [accepted] PHST- 2013/03/27 06:00 [entrez] PHST- 2013/03/27 06:00 [pubmed] PHST- 2013/06/19 06:00 [medline] AID - 10.1002/eji.201243040 [doi] PST - ppublish SO - Eur J Immunol. 2013 May;43(5):1173-84. doi: 10.1002/eji.201243040. Epub 2013 Apr 9.