title: Strategically localized dendritic cells promote rapid T cell responses to lymph-borne particulate antigens.
abstract: Upon infection, adaptive immune responses play catch-up with rapidly replicating pathogens. While mechanisms for efficient humoral responses to lymph-borne antigens have been characterized, the current paradigm for T cell responses to infections and particulate vaccines involves delayed migration of peripheral antigen-bearing dendritic cells (DCs) to lymph nodes (LNs), where they elicit effector T cell responses. Utilizing whole LN 3D imaging, histo-cytometry, and intravital 2-photon microscopy, we have identified a specialized population of DCs, enriched in the LN-resident CD11b(+) subset, which resides within the lymphatic sinus endothelium and scans lymph with motile dendrites. These DCs capture draining particles and present associated antigens to T lymphocytes, inducing T cell responses much sooner than and independently of migratory DCs. Thus, strategic DC subset positioning in LNs limits a potentially costly delay in generation of T cell responses to lymph-borne antigens, contributing to effective host defense. These findings are also highly relevant to vaccine design.
authors.affiliation: Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1892, USA. Electronic address: gernermy@niaid.nih.gov.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Gerner
authors.affiliation: Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1892, USA; Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892-1662, USA.
authors.forename: Parizad
authors.initials: P
authors.lastname: Torabi-Parizi
authors.affiliation: Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1892, USA. Electronic address: rgermain@nih.gov.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Germain
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology; D039481:CD11b Antigen / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D003712:Dendrites / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004729:Endothelium, Lymphatic / Q000276:immunology; D006801:Humans; D021621:Imaging, Three-Dimensional; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D052638:Particulate Matter / Q000276:immunology; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination
chemical_list: D000942:Antigens, Bacterial; D039481:CD11b Antigen; D052638:Particulate Matter