EBV-induced human CD8(+) NKT cells synergise CD4(+) NKT cells suppressing EBV-associated tumours upon induction of Th1-bias.
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.
Xiao
Wei
W
Laboratory of Allergy and Clinical Immunology, Institute of Allergy and Immune-related Diseases, Center for Medical Research, and Department of Immunology, Wuhan University School of Medicine, Wuhan, China.
Li
Li
L
Zhou
Rui
R
Xiao
Ruijing
R
Wang
Yujuan
Y
Ji
Xiang
X
Wu
Mengjun
M
Wang
Lan
L
Huang
Wei
W
Zheng
Xiaoling
X
Tan
Xinti
X
Chen
Lang
L
Xiong
Tao
T
Xiong
Jie
J
Jin
Youxin
Y
Tan
Jinquan
J
He
Yuling
Y
D019264:Adoptive Transfer; D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology*; D045744:Cell Line, Tumor; D002678:Chimera; D003602:Cytotoxicity, Immunologic; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006689:Hodgkin Disease / Q000150:complications / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000150:complications / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D009303:Nasopharyngeal Neoplasms / Q000150:complications / Q000276:immunology* / Q000628:therapy*; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
D015704:CD4 Antigens; D016827:CD8 Antigens; D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma