title: Neutrophils transport antigen from the dermis to the bone marrow, initiating a source of memory CD8+ T cells.
abstract: The bone marrow (BM) has been identified as a possible organ for T cell priming, yet the fundamental mechanisms of a polyclonal immune response in the BM remain unknown. We found that after intradermal injection of modified vaccinia Ankara virus, unexpected sources of newly primed polyclonal virus-specific CD8(+), but not CD4(+), T cells were localized in the BM and the draining lymph nodes (dLNs) prior to blood circulation. We identified neutrophils as the virus-carrier cells from the dermis to the BM. In both neutrophil-depleted and Ccr1(-/-) mice, virus-specific BM CD8(+) responses were lost. Myeloid antigen-presenting cells were required for BM CD8(+) T cell priming. A systems biology analysis of dLN and BM virus-specific CD8(+) T cells revealed distinct transcriptional and multifunctional profiles for cells primed in each organ. We provide direct evidence for how antigen is transported to the BM, providing a source of virus-specific memory CD8(+) T cells.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, INSERM UMR-S 945, Paris, France.
authors.forename: Darragh
authors.initials: D
authors.lastname: Duffy
authors.forename: Hélène
authors.initials: H
authors.lastname: Perrin
authors.forename: Valérie
authors.initials: V
authors.lastname: Abadie
authors.forename: Nora
authors.initials: N
authors.lastname: Benhabiles
authors.forename: Alexandre
authors.initials: A
authors.lastname: Boissonnas
authors.forename: Christelle
authors.initials: C
authors.lastname: Liard
authors.forename: Benjamin
authors.initials: B
authors.lastname: Descours
authors.forename: Damien
authors.initials: D
authors.lastname: Reboulleau
authors.forename: Olivia
authors.initials: O
authors.lastname: Bonduelle
authors.forename: Bernard
authors.initials: B
authors.lastname: Verrier
authors.forename: Nico
authors.initials: N
authors.lastname: Van Rooijen
authors.forename: Christophe
authors.initials: C
authors.lastname: Combadière
authors.forename: Béhazine
authors.initials: B
authors.lastname: Combadière
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D020405:Dermis / Q000276:immunology*; D005260:Female; D007156:Immunologic Memory / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D054389:Receptors, CCR1 / Q000276:immunology
chemical_list: D000941:Antigens; C515301:Ccr1 protein, mouse; D054389:Receptors, CCR1