EBV-induced Human CD8~+NKT Cells Suppress Tumorigenesis By EBV-associated Malignancies In Human-thymus-SCID Chimeras

Objective:NKT cells are unconventional glycolipid-reactive T cells that bridge innate and adaptive immunity. On encountering glycolipids, NKT cells promptly become activated to provide protection against infection and to regulate tumor immunity and autoimmunity. We show that the frequenciesof 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 humanthymus-severe combined immunodeficient (hu-thym-SCID) chimeras, EBV challenge efficiently promotes the generation of IFN-;-biased CD8+NKT cells. These cells are strongly cytotoxic, drive syngeneic T cells into a Thl bias, and enhance T-cell cytotoxicity to EBV-associated tumor cells. Human NKT cells in tumor immune surveillance, protection and inhibition of its potential to play a basic mechanism has not yet fully understood. So in this study we want to To further illustrate the role and mechanism of EBV-induced CD8+NKT cells in EB virus-related cancers.Methods:We constructed a human thymus of severe combined immunodeficiency (hu-thym-SCID) chimeric model, using Q-PCR and flow cytometry and examined: EBV-stimulated or HTLV-1 to stimulate hu-thym-SCID thymus immunodeficiency embedded fit in the natural killer T cell development and function, and further testing NKT cells subtypes. We also constructed HXTT H-T-SCID chimera model, monitoring tumor growth curve and survival rate of detection of the HXTT H-T-SCID chimera model of NKT cells in vivo secretion of cytokines, also discussed the stimulation of CD4+EBV NKT and CD8+NKT cells against EBV-related tumors in synergy. Results: In human thymus-SCID mouse chimera model, EB virus induced CD8+ NKT cells inhibit the EB virus-related cancer depends on the Thl response and offset CD3+T cells with the department. However, only adoptive transfer of CD4+NKT cells suppress T cell immunity. Interestingly, CD4+NKT cells to secrete high levels of IL-2, they will raise the adoptive transfer of CD8+NKT cells and T cell persistence, therefore chimera model, while adoptive transfer of CD4+NKT fine and CD8+NKT cells may provoke a more pronounced anti-tumor T cell response. Therefore, comprehensive view, EB virus induced CD4+and CD8+NKT cells to immune reconstitution synergistic T cell tumor immunity.Significance:In this study, through H-T-SCID chimera model and HXTT H-T-SCID chimera model, found that in EB virus related T cell immunity for tumor, EB virus specific CD8+NKT cells is necessary, a total transfer CD4+and CD8+NKT cells in chimeras, CD4+NKT cells in combination with CD8+NKT cells, leading to significant anti-tumor T cell response. The data suggest strongly that the immune reconstitution with EBV-induced CD8+NKT cells could be a useful strategy in management of EBV-associated malignancies.