title: Lung CD103+ dendritic cells efficiently transport influenza virus to the lymph node and load viral antigen onto MHC class I for presentation to CD8 T cells.
abstract: The uptake, transport, and presentation of Ags by lung dendritic cells (DCs) are central to the initiation of CD8 T cell responses against respiratory viruses. Although several studies have demonstrated a critical role of CD11b(low/neg)CD103(+) DCs for the initiation of cytotoxic T cell responses against the influenza virus, the underlying mechanisms for its potent ability to prime CD8 T cells remain poorly understood. Using a novel approach of fluorescent lipophilic dye-labeled influenza virus, we demonstrate that CD11b(low/neg)CD103(+) DCs are the dominant lung DC population transporting influenza virus to the posterior mediastinal lymph node as early as 20 h postinfection. By contrast, CD11b(high)CD103(neg) DCs, although more efficient for taking up the virus within the lung, migrate poorly to the lymph node and remain in the lung to produce proinflammatory cytokines instead. CD11b(low/neg)CD103(+) DCs efficiently load viral peptide onto MHC class I complexes and therefore uniquely possess the capacity to potently induce proliferation of naive CD8 T cells. In addition, the peptide transporters TAP1 and TAP2 are constitutively expressed at higher levels in CD11b(low/neg)CD103(+) DCs, providing, to our knowledge, the first evidence of a distinct regulation of the Ag-processing pathway in these cells. Collectively, these results show that CD11b(low/neg)CD103(+) DCs are functionally specialized for the transport of Ag from the lung to the lymph node and also for efficient processing and presentation of viral Ags to CD8 T cells.
authors: Immunology Programme, Centre for Life Sciences, National University of Singapore, Singapore 117456.
authors: Adrian W S
authors: AW
authors: Ho
authors: Nayana
authors: N
authors: Prabhu
authors: Richard John
authors: RJ
authors: Betts
authors: Moyar Qing
authors: MQ
authors: Ge
authors: Xilei
authors: X
authors: Dai
authors: Paul Edward
authors: PE
authors: Hutchinson
authors: Fei Chuin
authors: FC
authors: Lew
authors: Kok Loon
authors: KL
authors: Wong
authors: Brendon John
authors: BJ
authors: Hanson
authors: Paul A
authors: PA
authors: Macary
authors: David Michael
authors: DM
authors: Kemeny
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D039001:Integrin alpha Chains / Q000276:immunology; D008168:Lung / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009975:Orthomyxoviridae / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015703:Antigens, CD; D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I; D039001:Integrin alpha Chains; C091367:alpha E integrins