PMID- 25049334 OWN - NLM STAT- MEDLINE DCOM- 20140922 LR - 20211021 IS - 1540-9538 (Electronic) IS - 0022-1007 (Print) IS - 0022-1007 (Linking) VI - 211 IP - 8 DP - 2014 Jul 28 TI - Trans-nodal migration of resident dendritic cells into medullary interfollicular regions initiates immunity to influenza vaccine. PG - 1611-21 LID - 10.1084/jem.20132327 [doi] AB - 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. CI - (c) 2014 Woodruff et al. FAU - Woodruff, Matthew C AU - Woodruff MC AD - 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. FAU - Heesters, Balthasar A AU - Heesters BA AD - 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. FAU - Herndon, Caroline N AU - Herndon CN AD - The Program in Cellular and Molecular Medicine, Children's Hospital Boston, Boston, MA 02115. FAU - Groom, Joanna R AU - Groom JR AD - Department of Medical Biology, The Walter and Eliza Hall Institute of Medical Research, University of Melbourne, Parkville, Victoria 3052, Australia. FAU - Thomas, Paul G AU - Thomas PG AD - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105. FAU - Luster, Andrew D AU - Luster AD AD - 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. FAU - Turley, Shannon J AU - Turley SJ AD - 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. FAU - Carroll, Michael C AU - Carroll MC AD - 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. LA - eng GR - AI107625/AI/NIAID NIH HHS/United States GR - R37 AI054636/AI/NIAID NIH HHS/United States GR - P30 DK043351/DK/NIDDK NIH HHS/United States GR - P01 AI078897/AI/NIAID NIH HHS/United States GR - P01 AI045757/AI/NIAID NIH HHS/United States GR - R01 DK07/DK/NIDDK NIH HHS/United States GR - R01 CA069212/CA/NCI NIH HHS/United States GR - R01CA069212/CA/NCI NIH HHS/United States GR - 1 P01 AI078897/AI/NIAID NIH HHS/United States GR - R01 DK074500/DK/NIDDK NIH HHS/United States GR - R01 AI039246/AI/NIAID NIH HHS/United States GR - R01 AI107625/AI/NIAID NIH HHS/United States GR - T32 AI007498/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20140721 PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (Antigens, Viral) RN - 0 (Chemokines) RN - 0 (Cxcr3 protein, mouse) RN - 0 (Influenza Vaccines) RN - 0 (Receptors, CXCR3) SB - IM MH - Animals MH - Antigen Presentation/immunology MH - Antigens, Viral/immunology MH - B-Lymphocytes/immunology MH - CD4-Positive T-Lymphocytes/immunology MH - Cell Movement/*immunology MH - Chemokines/metabolism MH - Cluster Analysis MH - Dendritic Cells/*cytology MH - Immunity/*immunology MH - Immunologic Memory/immunology MH - Influenza Vaccines/*immunology MH - Lymph/metabolism MH - Lymph Nodes/*cytology MH - Lymphocyte Activation/immunology MH - Mice MH - Mice, Inbred C57BL MH - Orthomyxoviridae/physiology MH - Orthomyxoviridae Infections/immunology/prevention & control/virology MH - Receptors, CXCR3/metabolism MH - Species Specificity MH - Vaccination PMC - PMC4113935 EDAT- 2014/07/23 06:00 MHDA- 2014/09/23 06:00 PMCR- 2015/01/28 CRDT- 2014/07/23 06:00 PHST- 2014/07/23 06:00 [entrez] PHST- 2014/07/23 06:00 [pubmed] PHST- 2014/09/23 06:00 [medline] PHST- 2015/01/28 00:00 [pmc-release] AID - jem.20132327 [pii] AID - 20132327 [pii] AID - 10.1084/jem.20132327 [doi] PST - ppublish SO - J Exp Med. 2014 Jul 28;211(8):1611-21. doi: 10.1084/jem.20132327. Epub 2014 Jul 21.