Nishimura T, Iwakabe K, Sekimoto M, Ohmi Y, Yahata T, Nakui M, Sato T, Habu S, Tashiro H, Sato M, Ohta A
Section of Genetic Engineering, Research Center for Genetic Engineering and Cell Transplantation, Tokai University School of Medicine, Isehara, Japan.
J Exp Med. 1999 Sep 6;190(5):617-27. doi: 10.1084/jem.190.5.617.
The role of T helper type 1 (Th1) and Th2 cells in tumor immunity was investigated using Th cells induced from ovalbumin (OVA)-specific T cell receptor transgenic mice. Although Th1 cells exhibited stronger cytotoxicity than Th2 cells, both cell types completely eradicated tumors when transferred into mice bearing A20 tumor cells transfected with the OVA gene (A20-OVA). Th1 cells eradicated the tumor mass by inducing cellular immunity, whereas Th2 cells destroyed the tumor by inducing tumor necrosis. Both Th1 and Th2 cells required CD8(+) T cells to eliminate tumors, and neither of these cells were able to completely eliminate A20-OVA tumors from T and B cell-deficient RAG2(-/-) mice. Mice cured from tumors by Th1 and Th2 cell therapy rejected A20-OVA upon rechallenge, but CD8(+) cytotoxic T lymphocytes were induced only from spleen cells prepared from cured mice by Th1 cell therapy. Moreover, we demonstrated that Th1 and Th2 cells used distinct adhesion mechanisms during tumor eradication: the leukocyte function-associated antigen (LFA)-1-dependent cell-cell adhesion step was essential for Th1 cell therapy, but not for Th2 cell therapy. These findings demonstrated for the first time the distinct role of antigen-specific Th1 and Th2 cells during eradication of established tumors in vivo.
利用从卵清蛋白（OVA）特异性T细胞受体转基因小鼠诱导产生的Th细胞，研究了1型辅助性T细胞（Th1）和Th2细胞在肿瘤免疫中的作用。尽管Th1细胞比Th2细胞表现出更强的细胞毒性，但当将这两种细胞类型转移到携带用OVA基因转染的A20肿瘤细胞（A20-OVA）的小鼠体内时，它们都能完全根除肿瘤。Th1细胞通过诱导细胞免疫来根除肿瘤块，而Th2细胞则通过诱导肿瘤坏死来破坏肿瘤。Th1细胞和Th2细胞都需要CD8(+) T细胞来消除肿瘤，并且这两种细胞都无法从T和B细胞缺陷的RAG2(-/-)小鼠中完全消除A20-OVA肿瘤。通过Th1和Th2细胞疗法治愈肿瘤的小鼠在再次受到攻击时会排斥A20-OVA，但只有通过Th1细胞疗法从治愈小鼠制备的脾细胞中才能诱导出CD8(+) 细胞毒性T淋巴细胞。此外，我们证明Th1细胞和Th2细胞在根除肿瘤过程中使用了不同的黏附机制：白细胞功能相关抗原（LFA）-1依赖性细胞间黏附步骤对Th1细胞疗法至关重要，但对Th2细胞疗法并非如此。这些发现首次证明了抗原特异性Th1和Th2细胞在体内根除已建立肿瘤过程中的不同作用。
