Involvement of CD166 in the activation of human γδT cells by tumor cells sensitized with nonpeptide antigens
Involvement of CD166 in the activation of human γδT cells by tumor cells sensitized with nonpeptide antigens
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DOI：
10.4049/jimmunol.177.2.877
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发表时间：
2006-07-15
影响因子：
4.4
通讯作者：
Minato, Nagahiro
中科院分区：
文献类型：
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作者：
Kato, Yu;Tanaka, Yoshimasa;Minato, Nagahiro
我们之前报道过，人类 V gamma 2V delta 2-gamma delta T 细胞被帕米膦酸 (PAM) 处理的许多人类肿瘤细胞系以 γ delta TCR 依赖性方式激活。在本研究中，我们指出，合成的焦磷酸单酯Ag，2-甲基3-丁烯基-1-焦磷酸，可以直接“敏化”肿瘤细胞以独立于宿主代谢激活γδT细胞，而据报道PAM的敏化作用依赖于药理活性。一些未能被 PAM 致敏的特殊肿瘤细胞也无法通过 2-甲基-3-丁烯基-1-焦磷酸处理来激活 γ δ T 细胞，这表明除了非肽 Ag 之外，还需要宿主因子来有效激活 γ δ T 细胞。通过筛选针对大量肿瘤细胞系的单克隆抗体，我们发现 CD166 的表达与 PAM 治疗后激活 γ δ T 细胞的能力密切相关。用 CD166 cDNA 转染 CD166 阴性肿瘤细胞系，PAM 处理后激活 γ δ T 细胞的能力显着增强。相反，通过短发夹RNA下调携带CD166的肿瘤细胞系中的CD166表达导致PAM诱导的γδT细胞刺激活性显着降低。 γ δ T 细胞表达 CD6（CD166 的一种受体），并且 CD6 和 CD166 一起被募集到 γ δ T 细胞和 PAM 处理的肿瘤细胞之间的突触中心，与 γ δ TCR/CD3 共定位。结果表明，肿瘤细胞上 CD6 与 CD166 的结合在负载非肽 Ag 的肿瘤细胞激活 γ δ T 细胞中发挥着重要作用，无论是内源性还是外源性。
We previously reported that human V gamma 2V delta 2-gamma delta T cells were activated by many human tumor cell lines treated with pamidronate (PAM) in a gamma delta TCR-dependent manner. In the present study, we indicated that a synthetic pyrophosphomonoester Ag, 2-methy3-butenyl-1-pyrophosphate, could directly "sensitize" the tumor cells to activate gamma delta T cells independently of the host metabolism, while the sensitizing effect of PAM was reported to be dependent on the pharmacological activity. Some exceptional tumor cells that failed to be sensitized by PAM were incapable of activating gamma delta T cells by the treatment with 2-methy-3-butenyl-1-pyrophosphate either, suggesting a requirement of host factor(s) for the effective gamma delta T cell activation in addition to the nonpeptide Ags. By screening mAbs against a large panel of tumor cell lines, we found that the expression of CD166 closely paralleled the capacity of activating gamma delta T cells upon PAM treatment. The transfection of a CD166-negative tumor cell line with CD166 cDNA caused a marked enhancement of the capacity to activate gamma delta T cells following PAM treatment. On the contrary, down-regulation of the CD166 expression in a CD166-bearing tumor cell line by short hairpin RNA resulted in a significant reduction of PAM-induced gamma delta T cell-stimulatory activity. gamma delta T cells expressed CD6, a receptor of CD166, and CD6 and CD166 were recruited together to the center of synapse between gamma delta T cells and PAM-treated tumor cells, colocalizing with gamma delta TCR/CD3. The results suggested that the engagement of CD6 with CD166 on tumor cells played an important role in the gamma delta T cell activation by the tumor cells loaded with nonpeptide Ags either endogenously or exogenously.