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J Exp Med. 2014 Jul 28;211(8):1611-21. doi: 10.1084/jem.20132327. Epub 2014 Jul 21.

Trans-nodal migration of resident dendritic cells into medullary interfollicular regions initiates immunity to influenza vaccine.

Author information

1
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.
2
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.
3
The Program in Cellular and Molecular Medicine, Children's Hospital Boston, Boston, MA 02115.
4
Department of Medical Biology, The Walter and Eliza Hall Institute of Medical Research, University of Melbourne, Parkville, Victoria 3052, Australia.
5
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105.
6
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.
7
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.
8
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.

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.

PMID:
25049334
PMCID:
PMC4113935
DOI:
10.1084/jem.20132327
[Indexed for MEDLINE]
Free PMC Article

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