Tumor-specific CD4+ T cells develop cytotoxic activity and eliminate virus-induced tumor cells in the absence of regulatory T cells.
Tumor-specific CD4+ T cells develop cytotoxic activity and eliminate virus-induced tumor cells in the absence of regulatory T cells.
复制标题
DOI：
10.1007/s00262-012-1329-y
复制
发表时间：
2013-02
影响因子：
5.8
通讯作者：
Dittmer, Ulf
中科院分区：
文献类型：
--
作者：
Akhmetzyanova, Ilseyar;Zelinskyy, Gennadiy;Schimmer, Simone;Brandau, Sven;Altenhoff, Petra;Sparwasser, Tim;Dittmer, Ulf
肿瘤特异性细胞毒性 CD8+ T 细胞在肿瘤免疫控制中的重要作用已明确，但效应 CD4+ T 细胞的作用却知之甚少。在目前的研究中，我们使用C57BL/6小鼠来源的小鼠逆转录病毒诱导的肿瘤细胞系，即FBL-3细胞，作为模型来研究肿瘤形成过程中免疫控制和逃逸的基本机制。这项研究表明，肿瘤特异性 CD4+ T 细胞能够抵御病毒诱导的肿瘤细胞。我们在此表明，在肿瘤生长的早期阶段，肿瘤特异性 CD4+ T 细胞产生细胞因子和细胞毒性分子颗粒酶 B (GzmB) 的扩增。重要的是，我们证明，携带 FBL-3 的 DEREG 转基因小鼠体内调节性 T 细胞 (Treg) 和 CD8+ T 细胞的耗竭增强了 CD4+ T 细胞产生的 IL-2 和 GzmB，并增加了 FV 特异性 CD4+ T 细胞效应和细胞毒性反应，从而导致肿瘤完全消退。因此，肿瘤反应性CD4+T细胞获得的排斥肿瘤的能力很大程度上取决于Tregs的直接抑制活性。我们建议可以诱导细胞毒性 CD4+ T 细胞免疫反应，以增强对肿瘤病毒相关肿瘤的抵抗力。本文的在线版本 (doi:10.1007/s00262-012-1329-y) 包含补充材料，可供授权用户使用。
The important role of tumor-specific cytotoxic CD8+ T cells is well defined in the immune control of the tumors, but the role of effector CD4+ T cells is poorly understood. In the current research, we have used a murine retrovirus-induced tumor cell line of C57BL/6 mouse origin, namely FBL-3 cells, as a model to study basic mechanisms of immunological control and escape during tumor formation. This study shows that tumor-specific CD4+ T cells are able to protect against virus-induced tumor cells. We show here that there is an expansion of tumor-specific CD4+ T cells producing cytokines and cytotoxic molecule granzyme B (GzmB) in the early phase of tumor growth. Importantly, we demonstrate that in vivo depletion of regulatory T cells (Tregs) and CD8+ T cells in FBL-3-bearing DEREG transgenic mice augments IL-2 and GzmB production by CD4+ T cells and increases FV-specific CD4+ T-cell effector and cytotoxic responses leading to the complete tumor regression. Therefore, the capacity to reject tumor acquired by tumor-reactive CD4+ T cells largely depends on the direct suppressive activity of Tregs. We suggest that a cytotoxic CD4+ T-cell immune response may be induced to enhance resistance against oncovirus-associated tumors. The online version of this article (doi:10.1007/s00262-012-1329-y) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
32.4
作者：
Cao, Xuefang;Cai, Sheng F.;Ley, Timothy J.
通讯作者：
Ley, Timothy J.
影响因子：
3.6
作者：
Getnet D;Grosso JF;Goldberg MV;Harris TJ;Yen HR;Bruno TC;Durham NM;Hipkiss EL;Pyle KJ;Wada S;Pan F;Pardoll DM;Drake CG
通讯作者：
Drake CG
影响因子：
6.4
作者：
Erdman, Susan E.;Rao, Varada P.;Olipitz, Werner;Taylor, Christie L.;Jackson, Erin A.;Levkovich, Tatiana;Lee, Chung-Wei;Horwitz, Bruce H.;Fox, James G.;Ge, Zhongming;Poutahidis, Theofilos
通讯作者：
Poutahidis, Theofilos
DOI：
10.1084/jem.20050162
发表时间：
2005-10-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hegde NR;Dunn C;Lewinsohn DM;Jarvis MA;Nelson JA;Johnson DC
通讯作者：
Johnson DC
影响因子：
4.4
作者：
Hombach, Andreas;Koehler, Heike;Abken, Hinrich
通讯作者：
Abken, Hinrich