期刊
CELLULAR & MOLECULAR IMMUNOLOGY
卷 6, 期 5, 页码 367-379出版社
CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/cmi.2009.48
关键词
CD8(+) NKT cells; EBV; human-thymus-SCID chimaeras; IFN-gamma
类别
资金
- National Natural Science Foundation of China [30730054, 30572119, 30670937, 30971279, 30901363]
- Ministry of Science and Technology [2007AA02Z120]
- Ministry of Education, China [20060486008]
- National Innovation Experiment Program [WU2007061]
- Provincial Department of Science and Technology of Hubei, China [2007ABC010]
- Li Ka Shing Foundation, Hong Kong, China
CD8(+) natural killer T (NKT) cells from EBV-associated tumour patients are quantitatively and functionally impaired. EBV-induced CD8(+) NKT cells drive syngeneic T cells into a Th1-bias response to suppress EBV-associated malignancies. IL-4-biased CD4(+) NKT cells do not affect either syngeneic T cell cytotoxicity or Th cytokine secretion. Circulating mDC1 cells from patients with EBV-associated malignancies impair the production of IFN-gamma by CD8(+) NKT cells. In this study, we have established a human-thymus-SCID chimaera model to further investigate the underlying mechanism of EBV-induced CD8(+) NKT cells in suppressing EBV-associated malignancies. In the human-thymus-SCID chimera, EBV-induced CD8(+) NKT cells suppress EBV-associated malignancies in a manner dependent on the Th1-bias response and syngeneic CD3(+) T cells. However, adoptive transfer with CD4(+) NKT cells alone inhibits T cell immunity. Interestingly, CD4(+) NKT cells themselves secrete high levels of IL-2, enhancing the persistence of adoptively transferred CD8(+) NKT cells and T cells, thereby leading to a more pronounced T cell anti-tumour response in chimaeras co-transferred with CD4(+) and CD8(+) NKT cells. Thus, immune reconstitution with EBV-induced CD4(+) and CD8(+) NKT cells synergistically enhances T cell tumour immunity, providing a potential prophylactic and therapeutic treatment for EBV-associated malignancies. Cellular & Molecular Immunology. 2009;6(5):367-379.
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