title: Trans-nodal migration of resident dendritic cells into medullary interfollicular regions initiates immunity to influenza vaccine.
abstract: Dendritic cells (DCs) are well established as potent antigen-presenting cells critical to adaptive immunity. In vaccination approaches, appropriately stimulating lymph node-resident DCs (LNDCs) is highly relevant to effective immunization. Although LNDCs have been implicated in immune response, their ability to directly drive effective immunity to lymph-borne antigen remains unclear. Using an inactive influenza vaccine model and whole node imaging approaches, we observed surprising responsiveness of LNDC populations to vaccine arrival resulting in a transnodal repositioning into specific antigen collection sites within minutes after immunization. Once there, LNDCs acquired viral antigen and initiated activation of viral specific CD4(+) T cells, resulting in germinal center formation and B cell memory in the absence of skin migratory DCs. Together, these results demonstrate an unexpected stimulatory role for LNDCs where they are capable of rapidly locating viral antigen, driving early activation of T cell populations, and independently establishing functional immune response.
authors: Graduate Program in Immunology, Department of Pediatrics, and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115 The Program in Cellular and Molecular Medicine, Children's Hospital Boston, Boston, MA 02115.
authors: Matthew C
authors: MC
authors: Woodruff
authors: The Program in Cellular and Molecular Medicine, Children's Hospital Boston, Boston, MA 02115 Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, Netherlands.
authors: Balthasar A
authors: BA
authors: Heesters
authors: The Program in Cellular and Molecular Medicine, Children's Hospital Boston, Boston, MA 02115.
authors: Caroline N
authors: CN
authors: Herndon
authors: Department of Medical Biology, The Walter and Eliza Hall Institute of Medical Research, University of Melbourne, Parkville, Victoria 3052, Australia.
authors: Joanna R
authors: JR
authors: Groom
authors: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105.
authors: Paul G
authors: PG
authors: Thomas
authors: Graduate Program in Immunology, Department of Pediatrics, and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115 Division of Rheumatology, Allergy, and Immunology, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129.
authors: Andrew D
authors: AD
authors: Luster
authors: Graduate Program in Immunology, Department of Pediatrics, and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115Graduate Program in Immunology, Department of Pediatrics, and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115 Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02215.
authors: Shannon J
authors: SJ
authors: Turley
authors: Graduate Program in Immunology, Department of Pediatrics, and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115Graduate Program in Immunology, Department of Pediatrics, and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115 The Program in Cellular and Molecular Medicine, Children's Hospital Boston, Boston, MA 02115 michael.carroll@childrens.harvard.edu.
authors: Michael C
authors: MC
authors: Carroll
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D018925:Chemokines / Q000378:metabolism; D016000:Cluster Analysis; D003713:Dendritic Cells / Q000166:cytology*; D007109:Immunity / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D008196:Lymph / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009975:Orthomyxoviridae / Q000502:physiology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D054367:Receptors, CXCR3 / Q000378:metabolism; D013045:Species Specificity; D014611:Vaccination
chemical_list: D000956:Antigens, Viral; D018925:Chemokines; C515188:Cxcr3 protein, mouse; D007252:Influenza Vaccines; D054367:Receptors, CXCR3