Natural killer cells license dendritic cell cross-presentation of B lymphoma cell--associated antigens.
OBJECTIVE
Presentation of exogenous antigen by MHC class I molecules, or cross-presentation, is a property of dendritic cells, which is considered crucial for the priming of cytotoxic T-cell response to tumor antigens. However, the precise mechanisms of this process are not fully understood.


RESULTS
We show here in a human in vitro system, using B lymphoma cells as a tumor model, that the cross-presentation of cell-associated antigens to T cells by dendritic cells requires "help" from natural killer cells. When autologous dendritic cells that had taken up apoptotic B lymphoma cells and induced to a fully mature state were used to stimulate nonadherent cells of peripheral blood mononuclear cells from healthy donors, they induced strong cytotoxicity against B lymphoma cells in a HLA-A0201-restricted manner. The cells failed to induce cytotoxicity, however, when purified T cells were used as effector cells. Depletion of CD56+ cells, but not CD14+ or CD19+ cells, abrogated the cytotoxicity of nonadherent cells, showing that the help was provided by natural killer cells. Further, when natural killer cells were present in the cultures, a strong and persistent production of interleukin-18, but not interleukin-12 and interleukin-15, was observed. Blocking interleukin-18 significantly reduced the cytotoxicity of nonadherent cells against B lymphoma cells.


CONCLUSIONS
These results suggest that capture of tumor cells and a full maturation status of dendritic cells are not sufficient to cross-prime CD8 T cells. Effective cross-priming requires further activation of dendritic cells by natural killer cells and an abundant production of interleukin-18, which, along with other yet undefined mechanisms, contribute to the generation of CTL response against B-cell lymphoma.
Dao
Tao
T
Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA.
Gomez-Nunez
Marta
M
Antczak
Christophe
C
Kappel
Barry
B
Jaggi
Jaspreet Singh
JS
Korontsvit
Tatyana
T
Zakhaleva
Victoriya
V
Scheinberg
David A
DA
D019138:Antibodies, Blocking / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000032:analysis / Q000276:immunology*; D019002:CD56 Antigen / Q000032:analysis / Q000276:immunology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D045142:Cross-Priming / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D020382:Interleukin-18 / Q000037:antagonists & inhibitors / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008212:Lymphocyte Depletion; D016393:Lymphoma, B-Cell / Q000276:immunology*; D010587:Phagocytosis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D019138:Antibodies, Blocking; D000951:Antigens, Neoplasm; D019002:CD56 Antigen; D020382:Interleukin-18