| Objective:NKT cells are a class of T cell subsets. Through its semi-invariant Va24-Jαl8/Vβ11 (Vα14-Jα18, in mice) TCR, NKT cells recognize glycolipids presented by CD1d and then activate. Activated NKT cells produce large amounts of cytokines, which regulate innate and adaptive immunity. EB virus infection in healthy people is universal. EBV antibodies can be detected in about 90% of the serum of adult. EBV is one of the human cancer-causing viruses. The development and prognosis of Hodgkin's lymphoma and nasopharyngeal carcinoma are associated with EB virus infection. In tumor immunity, NKT cells play a protective and suppressive role. But its potential mechanism of action has not been fully clarified. As for its protection and inhibition role, whether the opposing effection can cross-regulate each other and form a new immunoregulatory axis remains to be further studied.Methods:We studied six Hodgkin's lymphoma (HL) patients, six patients with nasopharyngeal carcinoma (NPC),6 control normal subjects (healthy EBV seronegative individuals, CN) and six subjects with latent EBV infection (healthy EBV seropositive individuals, LEI). In this study, flow cytometry, real-time quantitative RT-PCR, ELISPOR, cytotoxicity detection were used to assess the frequency and cytokine production of CD8+ NKT and CD4+ NKT cell in peripheral blood, and compare the killing activity of various subsets of NKT cells on tumor cell. At the same time, we constructed human-thymus-SCID chimeras and humanized xenogeneic tumor-transplanted human-thymus-SCID chimeras model, by which we examine the killing activity of the CD4+ NKT cells and CD8+ NKT cells and compare the tumor growth and animal survival. Results; CD8+ NKT cells from EB virus-associated malignancies are impaired. The total number of NKT cells in peripheral blood mononuclear cells of LEI and CN subjects was higher than that of Hodgkin's lymphoma and nasopharyngeal carcinoma. About 15% to 30% NKT cells from LEI and CN subjects are CD8+ NKT cells, whereas CD8+NKT cells was less than 3% in Hodgkin's lymphoma and nasopharyngeal carcinoma (NPC) patients. CD8+ NKT from LEI and CN subjects expressed very high levels of IFN-y and low levels of IL-4, however CD8+NKT cells from Hodgkin lymphoma and NPC patients produce low levels of IFN-y. EB virus-induced CD8+ NKT cells suppress the EB virus-associated tumors. CD8+ NKT cells from LEI and CN subjects could effectively kill the a-Galcer challenged EB virus-associated Hodgkin's lymphoma and nasopharyngeal carcinoma cell line, but does not kill non-tumor cells. In HXTT h-T-S chimeras transferred with EBV-challenged thymus CD8+ NKT cells (+T +DC), the local size of tumors was 20mm3 in 10 weeks and animal survival rate was significantly increased:30% of the animals survived 20 weeks. All Hodgkin's lymphoma and NPC HXTT H-T-S chimeras that were transferred with combinations of EBV-challenged thymic CD4+ NKT and CD8+ NKT cells (+ T+ DC) survived even longer than 20 weeks and in which the tumor size maintained at 10 mm3 for 18 weeks。Significance:In this study, we compared the number and cell function of NKT cell subsets in peripheral blood of 24 subjects (including EBV-associated cancer patients and control normal individuals). Meanwhile we used human-thymus-SCID chimera model to study the function of EB virus-induced NKT cell subsets in EBV-associatec tumor immunity. The research data provide a novel insight into the role and related mechanisms of humen EB virus-induced NKT cells in turner immunity. For the treatment of EB virus-related malignancies, this research provided a useful treatment idea.
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