RRC ID 38449
Author Shimizu K, Asakura M, Fujii S.
Title Prolonged antitumor NK cell reactivity elicited by CXCL10-expressing dendritic cells licensed by CD40L+ CD4+ memory T cells.
Journal J Immunol
Abstract Immunotherapy using dendritic cells (DCs) has the potential to activate both T cells and NK cells. We previously demonstrated the long-lasting antitumor responses by NK cells following immunization with bone marrow-derived DCs. In the current study, we demonstrate that long-term antitumor NK responses require endogenous DCs and a subset of effector memory CD4(+) T (CD4(+) T(EM)) cells. One month after DC immunization, injection of a tumor into DC-immunized mice leads to an increase in the expression of CXCL10 by endogenous DCs, thus directing NK cells into the white pulp where the endogenous DCs bridged CD4(+) T(EM) cells and NK cells. In this interaction, CD4(+) T(EM) cells express CD40L, which matures the endogenous DCs, and produce cytokines, such as IL-2, which activates NK cells. These findings suggest that DC vaccination can sustain long-term innate NK cell immunity but requires the participation of the adaptive immune system.
Volume 186(10)
Pages 5927-37
Published 2011-5-15
DOI 10.4049/jimmunol.1003351
PII jimmunol.1003351
PMID 21460206
MeSH Adaptive Immunity Animals CD4-Positive T-Lymphocytes / cytology CD4-Positive T-Lymphocytes / immunology* CD4-Positive T-Lymphocytes / metabolism CD40 Ligand / analysis Cancer Vaccines / immunology Cell Line, Tumor Cells, Cultured Chemokine CXCL10 / biosynthesis Chemokine CXCL10 / genetics Chemokine CXCL10 / immunology* Cytokines / biosynthesis Cytokines / immunology Dendritic Cells / cytology Dendritic Cells / immunology* Dendritic Cells / metabolism Immunologic Memory Interleukin-2 / immunology Killer Cells, Natural / immunology* Mice Mice, Inbred C57BL Mice, Knockout Polymerase Chain Reaction Sarcoma, Experimental / immunology* Sarcoma, Experimental / prevention & control Signal Transduction T-Lymphocyte Subsets / immunology*
IF 4.886
Times Cited 16
Human and Animal Cells