Introduction of OX40 ligand into lymphoma cells elicits anti-lymphoma immunity in vivo
Introduction of OX40 ligand into lymphoma cells elicits anti-lymphoma immunity in vivo
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DOI：
10.1016/j.exphem.2004.11.013
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发表时间：
2005-03-01
影响因子：
2.6
通讯作者：
Uchiyama, T
中科院分区：
文献类型：
--
作者：
Kaneko, H;Hori, T;Uchiyama, T
objective. OX40是TNF受体超家族的成员，其配体（OX40L）在诱导和维持整合的T细胞免疫应答中起关键作用。OX40L的参与向T细胞递送共刺激信号。在这项研究中，我们研究了OX40L转染的小鼠T细胞淋巴瘤细胞系EL4的接种是否可以诱导小鼠的抗淋巴瘤免疫。将亲代EL4、OX40L转染的EL4（EL4-OX40L）和空白对照载体转染的EL4（EL4-mock）分别接种于雌性C57 BL/6小鼠，比较肿瘤大小、总生存率、脾细胞CTL活性和免疫组化。虽然亲本EL4和EL4-模拟物都快速生长，但EL4 - 0X40L被排斥或生长慢于亲本EL4或EL4-模拟物。用抗CD4或抗CD8单抗预处理小鼠可促进EL4-OX40L的生长，表明CD4（+）和CD8（+）T细胞均参与抗淋巴瘤免疫。免疫组化结果显示，EL4-OX40L肿瘤内有CD8（+）T细胞浸润。体外CTL试验表明，排斥EL4-OX40L的小鼠脾细胞对亲代EL4具有明显的杀伤活性。OX40L基因转染淋巴瘤细胞是诱导抗淋巴瘤免疫的有效途径。(c)2005年国际实验血液学学会。爱思唯尔公司出版
Objective. OX40, a member of the TNF receptor superfamily, and its ligand (OX40L) play crucial roles in induction and maintenance of integrated T cell immune response. Engagement of OX40L delivers a costimulatory signal to T cells. In this study, we investigated whether inoculation of OX40L-transfected EL4, a murine T cell lymphoma cell line, could induce anti-lymphoma immunity in mice.Materials and Methods. Female C57BL/6 mice were inoculated with 1 x 10(5) cells of parental EL4, OX40L-transfected EL4 (EL4-OX40L), or mock control vector-transfected EL4 (EL4-mock), and then the tumor size, overall survival, CTL activity of spleen cells, and the immunohistochemistry were compared.Results. While both parental EL4 and EL4-mock grew rapidly, EL4-OX40L was rejected or grew slower than parental EL4 or EL4-mock. Pretreatment of mice with either anti-CD4 or anti-CD8 mAb accelerated the growth of EL4-OX40L, suggesting that both CD4(+) and CD8(+) T cells were involved in anti-lymphoma immunity. The inmumohistochemical study revealed the infiltration of CD8(+) T cells into the tumor of EL4-OX40L. In vitro CTL assay demonstrated that spleen cells of mice that had rejected EL4-OX40L had significant cytotoxic activity against parental EL4.Conclusion. The gene transfer of OX40L into lymphoma cells is an eligible and efficient modality to induce anti-lymphoma immunity. (c) 2005 International Society for Experimental Hematology. Published by Elsevier Inc.