Neonatal and adult microglia cross-present exogenous antigens.
Some observations have suggested that cells from the central nervous system (CNS) could present exogenous antigens on major histocompatibility complex (MHC) class I molecules to CD8(+) T cells (a process called cross-presentation). Microglia are the major myeloid immunocompetent cells of the CNS. When activated, following the injury of the nervous parenchyma, they become fully competent antigen-presenting cells (APC) that prime CD4(+) T lymphocytes. We therefore tested the cross-presentation capacity of murine microglia. We report that a microglial cell line (C8-B4), neonatal microglia, and interestingly adult microglia cross-present soluble exogenous antigen (ovalbumin) to a OVA-specific CD8(+) T-cell hybridoma and cross-prime OVA-specific naive OT-1 CD8(+) T cells. In both these cases, C8-B4 and neonatal microglia cross-present OVA as well as peritoneal macrophages. Although cross-presentation by adult microglia is less efficient, it is increased by GM-CSF and CpG oligodeoxynucleotide (ODN) stimulation. Using microglial cells either exposed to an inhibitor of proteasome, lactacystin, or purified from TAP(-/-) mice, we demonstrate that the microglia cross-present antigen in proteasome- and TAP-dependant pathways, respectively. Last, microglia purified from adult mice injected intracerebrally with OVA efficiently stimulate OVA-specific CD8(+) T cells, thereby showing that microglia take up and process exogenous antigen into MHC class I in vivo. This first demonstration of the cross-presentation property of microglia offers novel therapeutic approaches to modulate CD8 T-cell responses in the brain.
Beauvillain
Celine
C
Inserm U564, Université Angers, Angers, F-49933, France.
Donnou
Sabrina
S
Jarry
Ulrich
U
Scotet
Mari
M
Gascan
Hugues
H
Delneste
Yves
Y
Guermonprez
Pierre
P
Jeannin
Pascale
P
Couez
Dominique
D
D000375:Aging / Q000276:immunology*; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000941:Antigens / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D005434:Flow Cytometry; D005805:Genes, MHC Class I / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D010641:Phenotype; D046988:Proteasome Endopeptidase Complex; D013601:T-Lymphocytes / Q000276:immunology
D000941:Antigens; D016827:CD8 Antigens; D010047:Ovalbumin; D046988:Proteasome Endopeptidase Complex