EBV LMP2A-specific T Cell Immune Responses Elicited by Dendritic Cells Loaded with LMP2A Protein  

作　　者：Yun Chen Hua Sun Genyan Liu Bing Wang Fang Wang Beicheng Sun Kun Yao 

机构地区：[1]Department of Microbiology and Immunology, Nanjing Medical University,Nanjing 210029, China [2]Liver Transplant Center, The 1st Affiliated Hospital of Nanjing MedicalUniversity, Nanjing 210029, China [3]Brown Foundation Institute of Molecular Medicine, University of TexasHealth Science Center at Houston, Houston, TX 77030, USA [4]Department of Laboratory Medicine, The 1 st Affiliated Hospital of NanjingMedical University, Nanjing 210029, China [5]Department of Microbiology and Immunology, Nanjing Medical University, Nanjing 210029, China

出　　处：《Cellular & Molecular Immunology》2009年第4期269-276,共8页中国免疫学杂志（英文版）

基　　金：Acknowledgements We thank Professor Xueguang Zhang （Soochow University, Suzhou, China） for kindly providing plasmid pGEZ, pHIT456, pHIT60 and 293T cell lines. This work was supported by the National Natural Science Foundation of China （No. 30772003 and No. 30170880）, Jiangsu Province＇s Outstanding Medical Academic Leader programme （RC2007057） and Science Development Foundation of Nanjing Medical University （NMUZ009）.

摘　　要：Type Ⅱ Epstein-Barr virus （EBV） associated malignancies such as nasopharyngeal carcinoma and non-Hodgkin＇s lymphomas consistently express latent membrane 2A （LMP2A） proteins, which have been suggested to be an ideal target for immunotherapy. In previous studies we have demonstrated that using LMP2A protein loaded dendritic cells, the most powerful antigen processing cells in the body can elicit specific and robust anti-tumor cellular immune response in vitro. In this paper, we further investigated the T cell profile of the anti-tumor immune response. We found that LMP2A specific CD4＋ and CD8＋ T cells could be stimulated by LMP2A protein loaded dendritic cells （DCs）. The Thl type immune response is dominant in the immune response mediated by LMP2A specific CD4^＋ T cells. The CD8^＋ cytotoxic T cells can lyse LMP2A bearing cells effectively and specifically. The CD8^＋ cytotoxic T cells can also secrete high level of intracellular IFN-γ, which indicates these cells are EBV-LMP2A specific cytotoxic T cells. Altogether, our studies proved that LMP2A protein loaded DCs can elicit anti-tumor cellular immune responses efficiently. This study provides a rationale for the DC-based immunotherapy against EBV-LMP2A expressing malignancies.Type Ⅱ Epstein-Barr virus （EBV） associated malignancies such as nasopharyngeal carcinoma and non-Hodgkin＇s lymphomas consistently express latent membrane 2A （LMP2A） proteins, which have been suggested to be an ideal target for immunotherapy. In previous studies we have demonstrated that using LMP2A protein loaded dendritic cells, the most powerful antigen processing cells in the body can elicit specific and robust anti-tumor cellular immune response in vitro. In this paper, we further investigated the T cell profile of the anti-tumor immune response. We found that LMP2A specific CD4＋ and CD8＋ T cells could be stimulated by LMP2A protein loaded dendritic cells （DCs）. The Thl type immune response is dominant in the immune response mediated by LMP2A specific CD4^＋ T cells. The CD8^＋ cytotoxic T cells can lyse LMP2A bearing cells effectively and specifically. The CD8^＋ cytotoxic T cells can also secrete high level of intracellular IFN-γ, which indicates these cells are EBV-LMP2A specific cytotoxic T cells. Altogether, our studies proved that LMP2A protein loaded DCs can elicit anti-tumor cellular immune responses efficiently. This study provides a rationale for the DC-based immunotherapy against EBV-LMP2A expressing malignancies.

关 键 词：Epstein-Barr virus latent membrane 2 dendritic cell CYTOTOXICITY 

分 类 号：Q25[生物学—细胞生物学] S852.4[农业科学—基础兽医学]