NDLI: Innate NKT lymphocytes confer superior adaptive immunity via tumor-capturing dendritic cells

Content Provider	PubMed Central
Author	Liu, Kang Idoyaga, Juliana Charalambous, Anna Fujii, Shin-ichiro Bonito, Anthony Jose, Mordoh Rosa, Wainstok Bai, Xue-feng Liu, Yang Steinman, Ralph M.
Abstract	If irradiated tumor cells could be rendered immunogenic, they would provide a safe, broad, and patient-specific array of antigens for immunotherapies. Prior approaches have emphasized genetic transduction of live tumor cells to express cytokines, costimulators, and surrogate foreign antigens. We asked if immunity could be achieved by delivering irradiated, major histocompatibility complex–negative plasmacytoma cells to maturing mouse dendritic cells (DCs) within lymphoid organs. Tumor cells injected intravenously (i.v.) were captured by splenic DCs, whereas subcutaneous (s.c.) injection led only to weak uptake in lymph node or spleen. The natural killer T (NKT) cells mobilizing glycolipid α-galactosyl ceramide, used to mature splenic DCs, served as an effective adjuvant to induce protective immunity. This adjuvant function was mimicked by a combination of poly IC and agonistic αCD40 antibody. The adjuvant glycolipid had to be coadministered with tumor cells i.v. rather than s.c. Specific resistance was generated both to a plasmacytoma and lymphoma. The resistance afforded by a single vaccination lasted >2 mo and required both CD4 + and CD8 + T cells. Mature tumor capturing DCs stimulated the differentiation of P1A tumor antigen-specific, CD8 + T cells and uniquely transferred tumor resistance to naive mice. Therefore, the access of dying tumor cells to DCs that are maturing to activated NKT cells efficiently induces long-lived adaptive resistance.
Related Links	http://dx.doi.org/10.1084/jem.20050956
Ending Page	1516
Page Count	10
Starting Page	1507
File Format	PDF
ISSN	00221007
e-ISSN	15409538
Journal	The Journal of Experimental Medicine
Issue Number	11
Volume Number	202
Language	English
Publisher	The Rockefeller University Press
Publisher Date	2005-12-05
Access Restriction	Open
Rights Holder	The Rockefeller University Press
Subject Keyword	Immunology Immunology and Allergy Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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