Natural killer cells license dendritic cell cross-presentation of B lymphoma cell-associated antigens Journal Article
| Authors: | Dao, T.; Gómez-Nuñez, M.; Antczak, C.; Kappel, B.; Jaggi, J. S.; Korontsvit, T.; Zakhaleva, V.; Scheinberg, D. A. |
| Article Title: | Natural killer cells license dendritic cell cross-presentation of B lymphoma cell-associated antigens |
| Abstract: | Purpose: 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. Experimental Design and 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 non-adherent 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. © 2005 American Association for Cancer Research. |
| Keywords: | controlled study; human cell; t lymphocyte; dendritic cell; cytotoxicity; cell line, tumor; tumor antigen; b cell lymphoma; lymphoma, b-cell; antigen presentation; dendritic cells; immune response; antigens, neoplasm; lymphoma cell; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; natural killer cell; killer cells, natural; cytokine production; effector cell; cytotoxicity, immunologic; phagocytosis; cell stimulation; lymphocyte depletion; interleukin 12; interleukin 15; cd19 antigen; cd14 antigen; peripheral blood mononuclear cell; major histocompatibility antigen class 1; coculture techniques; interleukin 18; antibodies, blocking; cross presentation; cross-priming; cd56 antigen; antigens, cd56; interleukin-18 |
| Journal Title: | Clinical Cancer Research |
| Volume: | 11 |
| Issue: | 24 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2005-12-15 |
| Start Page: | 8763 |
| End Page: | 8772 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-05-0975 |
| PUBMED: | 16361564 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 7" - "Export Date: 24 October 2012" - "CODEN: CCREF" - "Source: Scopus" |
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MSK Authors
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21Jaggi -
11
Gomez -
499Scheinberg -
81Dao -
40Antczak -
29
Zakhaleva -
53Korontsvit -
28
Kappel
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