EBV-Induced Human CD8^＋ NKT Cells Synergise CD4^＋ NKT Cells Suppressing EBV-Associated Tumours upon Induction of Thl-Bias  

作　　者：Wei Xiao Li Li Rui Zhou Ruijing Xiao Yujuan Wang Xiang Ji Mengjun Wu Lan Wang Wei Huang Xiaoling Zheng Xinti Tan Lang Chen Tao Xiong Jie Xiong Youxin Jin Jinquan Tan Yuling He 

机构地区：[1]Laboratory of Allergy and Clinical Immunology, Institute of Allergy andImmune-related Diseases, Center for Medical Research, and Department ofImmunology, Wuhan University School of Medicine, Wuhan, China [2]Section of Geriatrics, Department of Internal Medicine, the Renmin Hospital,Wuhan University, Wuhan, China [3]The State Key Laboratory of Molecular Biology, Institute of Biochemistryand Cell Biology, Shanghai Institutes for Biological Sciences, ChineseAcademy of Science, Shanghai, China [4]These authors contributed equally to this work [5]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, Dong Hu Road 185, Wuchang 430071, Wuhan, China

出　　处：《Cellular & Molecular Immunology》2009年第5期367-379,共13页中国免疫学杂志（英文版）

基　　金：Acknowledgements This work was supported by the grants from the National Natural Science Foundation of China （30730054, 30572119, 30670937, 30971279, 30901363）, the Hi-tech Research and Development Program of China from Ministry of Science and Technology （2007AA02Z120）, the Ministry of Education （20060486008）, National Innovation Experiment Program for College Students （WU2007061）, Provincial Departrnent of Science and Technology of Hubei （2007ABC010）, China, and Chang Jiang Scholars Program from Ministry of Education, China and Li Ka Shing Foundation, Hong Kong, China （Chang Jiang Scholar T.J.）.

摘　　要：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 Thl-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-T 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 Thl-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.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 Thl-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-T 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 Thl-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.

关 键 词：CD8^＋ NKT cells EBV human-thymus-SCID chimaeras IFN-γ 

分 类 号：S943.112[农业科学—水产养殖] Q939.4[农业科学—水产科学]