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EBV-induced human CD8(+) NKT cells synergise CD4(+) NKT cells suppressing EBV-associated tumours upon induction of Th1-bias.

Abstract：

: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.

journal_name

Cell Mol Immunol

journal_title

Cellular & molecular immunology

authors

Xiao W,Li L,Zhou R,Xiao R,Wang Y,Ji X,Wu M,Wang L,Huang W,Zheng X,Tan X,Chen L,Xiong T,Xiong J,Jin Y,Tan J,He Y

doi

10.1038/cmi.2009.48

subject

Has Abstract

pub_date

2009-10-01 00:00:00

pages

367-79

issue

5

eissn

1672-7681

issn

2042-0226

journal_volume

6

pub_type

杂志文章

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