CD137-guided isolation and expansion of antigen-specific CD8 cells for potential use in adoptive immunotherapy
CD137-guided isolation and expansion of antigen-specific CD8 cells for potential use in adoptive immunotherapy
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DOI：
10.1007/s12185-008-0134-z
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发表时间：
2008-10-01
影响因子：
2.1
通讯作者：
Akatsuka, Yoshiki
中科院分区：
文献类型：
--
作者：
Watanabe, Kazue;Suzuki, Susumu;Akatsuka, Yoshiki
抗原特异性T细胞的有效分离和体外扩增是针对不可控感染和癌症的成功过继免疫治疗的关键。已经报道了几种用于这一目的的方法，例如，使用MHC-多聚体复合体、干扰素-γ分泌和针对T细胞表面表达的分子的抗体，包括CD25、CD69、CD107a、CD137和CD154。在后者中，CD137被认为是最有前景的靶点之一，因为它只在CD8(+)T细胞上表达，而在静止细胞上几乎检测不到。然而，基于CD137的方法与其他方法之间的详细比较尚未进行。因此，在这项研究中，我们比较了三种方法(与CD137、CD107a和四聚体)，使用HLA-A24限制性CMV pp65和EBV BRLF1表位作为模型抗原。我们发现，基于CD137的抗原刺激的CD8(+)T细胞的分离在纯度方面与基于四聚体的分选方法相当，而在随后的细胞扩增方面优于其他两种方法。该方法不太适用于CD4(+)T细胞，因为它们的CD137上调幅度不够高。总的来说，在分离和扩增抗原特异性CD8(+)细胞的测试方法中，这种方法最有可能是最佳的。
The efficient isolation and ex vivo expansion of antigen-specific T cells are crucial for successful adoptive immunotherapy against uncontrollable infections and cancers. Several methods have been reported for this purpose, for example, employing MHC-multimeric complexes, interferon-gamma secretion, and antibodies specific for molecules expressed on T-cell surfaces, including CD25, CD69, CD107a, CD137, and CD154. Of the latter, CD137 has been shown to be one of the most promising targets since it is only expressed on CD8(+) T cells early after encountering antigen, while being almost undetectable on resting cells. However, detailed comparisons between CD137-based and other methods have not yet been conducted. In this study, we therefore compared three approaches (with CD137, CD107a, and tetramers) using HLA-A24-restricted CMV pp65 and EBV BRLF1 epitopes as model antigens. We found that the CD137-based isolation of antigen-stimulated CD8(+) T cells was comparable to tetramer-based sorting in terms of purity and superior to the other two methods in terms of subsequent cell expansion. The method was less applicable to CD4(+) T cells since their CD137 upregulation is not sufficiently high. Collectively, this approach is most likely to be optimal among the methods tested for the isolation and expansion of antigen-specific CD8(+) cells.