CMV-independent lysis of glioblastoma by ex vivo expanded/activated Vδ1+ γδ T cells.
CMV-independent lysis of glioblastoma by ex vivo expanded/activated Vδ1+ γδ T cells.
复制标题
DOI：
10.1371/journal.pone.0068729
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lamb LS
中科院分区：
文献类型：
--
作者：
Knight A;Arnouk H;Britt W;Gillespie GY;Cloud GA;Harkins L;Su Y;Lowdell MW;Lamb LS
Vδ 2-γδ T细胞是抗CMV感染的重要效应细胞，其中Vδ1+ γδ T细胞是迄今为止最大的亚群。恶性胶质瘤通常含有CMV遗传物质和蛋白质，有证据表明CMV感染可能与多形性胶质母细胞瘤（GBM）的发生和/或进展有关。我们试图确定Vδ1+ γδ T细胞是否对GBM具有细胞毒性以及它们的细胞毒性依赖于CMV的程度。我们检查了来自健康CMV血清阳性和CMV血清阴性供体的离体扩增/活化的Vδ1+ γδ T细胞对未操作和CMV感染的已建立的GBM细胞系和从原发性肿瘤的短期培养物发育的细胞系的细胞毒性作用。扩增/活化的Vδ1+ T细胞杀死CMV阴性U251、U87和U373 GBM细胞系和两个原发性肿瘤外植体，而不管供体的血清学状态如何。实验性CMV感染不增加Vδ1+ T细胞介导的细胞毒性，并且在某些情况下，当用CMV感染时，细胞系对裂解更具抗性。CMV感染细胞系的流式细胞术分析显示，CMV感染细胞中NKG 2D配体ULBP-2和ULBP-3以及云母/B下调。这些研究表明，无论是否存在CMV感染，离体扩增/活化的Vδ1+ γδ T细胞都容易识别并杀死已建立的GBM细胞系和原代肿瘤来源的GBM细胞，然而，CMV可能增强GBM细胞系对先天识别的抗性，这可能导致GBM的免疫原性差。
Vδ2neg γδ T cells, of which Vδ1+ γδ T cells are by far the largest subset, are important effectors against CMV infection. Malignant gliomas often contain CMV genetic material and proteins, and evidence exists that CMV infection may be associated with initiation and/or progression of glioblastoma multiforme (GBM). We sought to determine if Vδ1+ γδ T cells were cytotoxic to GBM and the extent to which their cytotoxicity was CMV dependent. We examined the cytotoxic effect of ex vivo expanded/activated Vδ1+ γδ T cells from healthy CMV seropositive and CMV seronegative donors on unmanipulated and CMV-infected established GBM cell lines and cell lines developed from short- term culture of primary tumors. Expanded/activated Vδ1+ T cells killed CMV-negative U251, U87, and U373 GBM cell lines and two primary tumor explants regardless of the serologic status of the donor. Experimental CMV infection did not increase Vδ1+ T cell - mediated cytotoxicity and in some cases the cell lines were more resistant to lysis when infected with CMV. Flow cytometry analysis of CMV-infected cell lines revealed down-regulation of the NKG2D ligands ULBP-2, and ULBP-3 as well as MICA/B in CMV-infected cells. These studies show that ex vivo expanded/activated Vδ1+ γδ T cells readily recognize and kill established GBM cell lines and primary tumor-derived GBM cells regardless of whether CMV infection is present, however, CMV may enhance the resistance GBM cell lines to innate recognition possibly contributing to the poor immunogenicity of GBM.
登录
查看更多内容
影响因子：
4.8
作者：
Lamb, LS;Musk, P;Henslee-Downey, PJ
通讯作者：
Henslee-Downey, PJ
影响因子：
15.9
作者：
Bryant, Nichole L.;Suarez-Cuervo, Catalina;Lamb, Lawrence S., Jr.
通讯作者：
Lamb, Lawrence S., Jr.
影响因子：
5.4
作者：
Cavanaugh, VJ;Deng, YP;Campbell, AE
通讯作者：
Campbell, AE
影响因子：
15.9
作者：
Déchanet, J;Merville, P;Moreau, JF
通讯作者：
Moreau, JF
影响因子：
4.5
作者：
Lamb, LS;Gee, AP;Henslee-Downey, PJ
通讯作者：
Henslee-Downey, PJ