How Do CD4(+) T Cells Detect and Eliminate Tumor Cells That Either Lack or Express MHC Class II Molecules?
How Do CD4(+) T Cells Detect and Eliminate Tumor Cells That Either Lack or Express MHC Class II Molecules?
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DOI：
10.3389/fimmu.2014.00174
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发表时间：
2014
影响因子：
7.3
通讯作者：
Bogen B
中科院分区：
文献类型：
--
作者：
Haabeth OA;Tveita AA;Fauskanger M;Schjesvold F;Lorvik KB;Hofgaard PO;Omholt H;Munthe LA;Dembic Z;Corthay A;Bogen B
即使在不存在CD 8 + T细胞的情况下，CD 4 + T细胞也有助于肿瘤根除。细胞毒性CD 4 + T细胞可直接杀伤MHC II类阳性肿瘤细胞。更令人惊讶的是，CD 4 + T细胞可以间接消除缺乏MHC II类表达的肿瘤细胞。本文就CD 4 + T细胞直接和间接介导的肿瘤细胞清除机制作一综述。重点是T细胞受体（TCR）转基因模型，其中可以跟踪具有特定特异性的幼稚CD 4 + T细胞的抗肿瘤反应。可以暂时作一些概括。对于MHCIIPOS和MHCIINEG肿瘤，由宿主抗原呈递细胞（APC）呈递肿瘤特异性抗原似乎是CD 4 + T细胞引发所需的。这已经在骨髓瘤模型（MOPC 315）中进行了广泛研究，其中肿瘤引流淋巴结中的宿主APC用分泌的肿瘤抗原致敏。在抗原识别后，初始CD 4 + T细胞分化为Th 1细胞并迁移到肿瘤。在肿瘤部位，MHCIIPOS和MHCIINEG肿瘤细胞的消除机制不同。在TCR转基因B16黑素瘤模型中，MHCIIPOS黑素瘤细胞以穿孔素/颗粒酶B依赖性方式被细胞毒性CD 4 + T细胞直接杀死。相比之下，MHCIINEG骨髓瘤细胞被IFN-γ刺激的M1样巨噬细胞杀死。总之，虽然MHCIIPOS和MHCIINEG肿瘤的CD 4 + T细胞的引发期似乎相似，但杀伤机制不同。未解决的问题和未来的研究方向得到解决。
CD4+ T cells contribute to tumor eradication, even in the absence of CD8+ T cells. Cytotoxic CD4+ T cells can directly kill MHC class II positive tumor cells. More surprisingly, CD4+ T cells can indirectly eliminate tumor cells that lack MHC class II expression. Here, we review the mechanisms of direct and indirect CD4+ T cell-mediated elimination of tumor cells. An emphasis is put on T cell receptor (TCR) transgenic models, where anti-tumor responses of naïve CD4+ T cells of defined specificity can be tracked. Some generalizations can tentatively be made. For both MHCIIPOS and MHCIINEG tumors, presentation of tumor-specific antigen by host antigen-presenting cells (APCs) appears to be required for CD4+ T cell priming. This has been extensively studied in a myeloma model (MOPC315), where host APCs in tumor-draining lymph nodes are primed with secreted tumor antigen. Upon antigen recognition, naïve CD4+ T cells differentiate into Th1 cells and migrate to the tumor. At the tumor site, the mechanisms for elimination of MHCIIPOS and MHCIINEG tumor cells differ. In a TCR-transgenic B16 melanoma model, MHCIIPOS melanoma cells are directly killed by cytotoxic CD4+ T cells in a perforin/granzyme B-dependent manner. By contrast, MHCIINEG myeloma cells are killed by IFN-γ stimulated M1-like macrophages. In summary, while the priming phase of CD4+ T cells appears similar for MHCIIPOS and MHCIINEG tumors, the killing mechanisms are different. Unresolved issues and directions for future research are addressed.
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影响因子：
11.4
作者：
BOGEN, B;LAMBRIS, JD
通讯作者：
LAMBRIS, JD
影响因子：
158.5
作者：
Dave, SS;Wright, G;Staudt, LM
通讯作者：
Staudt, LM
影响因子：
2.9
作者：
EISEN, HN;SIMMS, ES;POTTER, M
通讯作者：
POTTER, M
影响因子：
4
作者：
Barnden, MJ;Allison, J;Carbone, FR
通讯作者：
Carbone, FR
影响因子：
5.4
作者：
BOGEN, B;MALISSEN, B;HAAS, W
通讯作者：
HAAS, W