Journal
JOURNAL OF IMMUNOLOGY
Volume 186, Issue 10, Pages 5927-5937Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1003351
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- Ministry of Education, Culture, Sports, Science, and Technology of Japan
- Grants-in-Aid for Scientific Research [23380186, 21590546] Funding Source: KAKEN
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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. The Journal of Immunology, 2011, 186: 5927-5937.
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