title: EBV-induced human CD8+ NKT cells suppress tumorigenesis by EBV-associated malignancies.
abstract: The underlying mechanism of the protective and suppressive role of NKT cells in human tumor immunosurveillance remains to be fully elucidated. We show that the frequencies of CD8(+) NKT cells in patients with EBV-associated Hodgkin's lymphoma or nasopharyngeal carcinoma are significantly lower than those in healthy EBV carriers. These CD8(+) NKT cells in tumor patients are also functionally impaired. In human-thymus-severe combined immunodeficient (hu-thym-SCID) chimeras, EBV challenge efficiently promotes the generation of IFN-gamma-biased CD8(+) NKT cells. These cells are strongly cytotoxic, drive syngeneic T cells into a Th1 bias, and enhance T-cell cytotoxicity to EBV-associated tumor cells. Interleukin-4-biased CD4(+) NKT cells are predominately generated in unchallenged chimeras. These cells are noncytotoxic, drive syngeneic T cells into a Th2 bias, and do not affect T-cell cytotoxicity. In humanized xenogeneic tumor-transplanted hu-thym-SCID chimeras, adoptive transfer with EBV-induced CD8(+) NKT cells significantly suppresses tumorigenesis by EBV-associated malignancies. EBV-induced CD8(+) NKT cells are necessary and sufficient to enhance the T-cell immunity to EBV-associated malignancies in the hu-thym-SCID chimeras. CD4(+) NKT cells are synergetic with CD8(+) NKT cells, leading to a more pronounced T-cell antitumor response in the chimeras cotransferred with CD4(+) and CD8(+) NKT cells. Thus, immune reconstitution with EBV-induced CD8(+) NKT cells could be a useful strategy in management of EBV-associated malignancies.
authors.affiliation: Department of Immunology, and Laboratory of Allergy and Clinical Immunology, Institute of Allergy and Immune-related Diseases, Center for Medical Research, Wuhan University School of Medicine, Wuhan, People's Republic of China.
authors.forename: He
authors.initials: H
authors.lastname: Yuling
authors.forename: Xiao
authors.initials: X
authors.lastname: Ruijing
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Ji
authors.initials: J
authors.lastname: Xiang
authors.forename: Zhou
authors.initials: Z
authors.lastname: Rui
authors.forename: Wang
authors.initials: W
authors.lastname: Yujuan
authors.forename: Zhang
authors.initials: Z
authors.lastname: Lijun
authors.forename: Du
authors.initials: D
authors.lastname: Chunxian
authors.forename: Tan
authors.initials: T
authors.lastname: Xinti
authors.forename: Xiao
authors.initials: X
authors.lastname: Wei
authors.forename: Chen
authors.initials: C
authors.lastname: Lang
authors.forename: Jiang
authors.initials: J
authors.lastname: Yanping
authors.forename: Xiong
authors.initials: X
authors.lastname: Tao
authors.forename: Wu
authors.initials: W
authors.lastname: Mengjun
authors.forename: Xiong
authors.initials: X
authors.lastname: Jie
authors.forename: Jin
authors.initials: J
authors.lastname: Youxin
authors.forename: Tan
authors.initials: T
authors.lastname: Jinquan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002678:Chimera / Q000276:immunology; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006689:Hodgkin Disease / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D009303:Nasopharyngeal Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma