EBV LMP2A-specific T Cell Immune Responses Elicited by Dendritic Cells Loaded with LMP2A Protein
EBV LMP2A-specific T Cell Immune Responses Elicited by Dendritic Cells Loaded with LMP2A Protein
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DOI：
10.1038/cmi.2009.36
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发表时间：
2009-08
影响因子：
24.1
通讯作者：
Yun Chen;Hua Sun;Genyan Liu;B. Wang;F. Wang;Beicheng Sun;K. Yao
中科院分区：
文献类型：
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作者：
Yun Chen;Hua Sun;Genyan Liu;B. Wang;F. Wang;Beicheng Sun;K. Yao
Ⅱ型EB病毒（EBV）相关的恶性肿瘤如鼻咽癌和非霍奇金淋巴瘤持续表达潜伏膜2A（LMP 2A）蛋白，其已被认为是免疫治疗的理想靶点。在以前的研究中，我们已经证明，使用负载LMP 2A蛋白的树突状细胞，体内最强大的抗原加工细胞可以在体外引发特异性和强大的抗肿瘤细胞免疫应答。在本文中，我们进一步研究了抗肿瘤免疫应答的T细胞谱。我们发现负载LMP 2A蛋白的树突状细胞（DCs）可以刺激LMP 2A特异性的CD 4+和CD 8 + T细胞。Th 1型免疫应答在LMP 2A特异性CD 4 + T细胞介导的免疫应答中占主导地位。CD 8+细胞毒性T细胞可以有效和特异性地裂解携带LMP 2A的细胞。CD 8+细胞毒性T细胞还可以分泌高水平的细胞内IFN-γ，这表明这些细胞是EBV-LMP 2A特异性细胞毒性T细胞。总之，我们的研究证明负载LMP 2A蛋白的DC可以有效地诱导抗肿瘤细胞免疫应答。该研究为基于DC的针对表达EBV-LMP 2A的恶性肿瘤的免疫疗法提供了理论基础。
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 Th1 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.