Adenovirus serotype 5 E1A expressing tumor cells elicit a tumor-specific CD8+ T cell response independent of NKG2D.
Adenovirus serotype 5 E1A expressing tumor cells elicit a tumor-specific CD8+ T cell response independent of NKG2D.
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腺病毒血清型5 E1A表达肿瘤细胞引起独立于NKG2D的肿瘤特异性CD8+ T细胞反应。
DOI：
10.1016/j.rinim.2015.01.001
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Routes JM
中科院分区：
文献类型：
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作者：
Korrer MJ;Routes JM
腺病毒血清型2或血清型5（Ad 2/5）E1 A基因在肿瘤细胞中的表达上调NKG 2D活化受体（在NK细胞和T细胞上表达）识别的配体，并降低其致瘤性，这是一个依赖于NK细胞和T细胞的过程。在一些模型系统中，NKG 2D配体在肿瘤细胞上的强制过表达诱导了介导抗肿瘤免疫的抗原特异性CD 8 + T细胞。我们想确定表达E1 A的肿瘤细胞上的NKG 2D配体与免疫细胞上的NKG 2D的相互作用是否有助于E1 A诱导CD 8 + T细胞抗肿瘤应答或降低致瘤性的能力。为了解决这些问题，我们使用表达Ad 5 E1 A（MCA-205-E1 A细胞）的MCA-205肿瘤细胞系或MCA-205细胞，E1 A和卵清蛋白（MCA-205-E1 A-OVA）或OVA（MCA-205-OVA）的融合蛋白。我们发现E1 A或E1 A-OVA的表达上调MCA-205细胞表面NKG 2D配体RAE-1的表达，但不上调OVA。此外，在WT B6小鼠中，MCA-205-E1 A细胞和MCA-205-E1 A-OVA细胞比MCA-205或MCA-205-OVA细胞对NK细胞裂解更敏感，但在NKG 2D缺陷型B6小鼠中则不然。接下来，我们将WT或NKG 2D缺陷型OT-1 T细胞（识别OVA残基257-264的CD 8 T细胞）分别过继转移到WT B6小鼠或NKG 2D缺陷型B6小鼠中，并测量用MCA-205-E1 A-OVA或MCA-205-OVA细胞免疫后OT-1细胞的扩增。我们发现，在B6小鼠中，表达OVA的MCA-205细胞系免疫后OT-1细胞的扩增不受NKG 2D存在或不存在的影响。最后，我们发现，与WT B6小鼠相比，E1 A降低MCA-205细胞致瘤性的能力在B6-NKG 2D缺陷小鼠中未受损。我们的研究结果表明，E1 A降低MCA-205细胞致瘤性或诱导抗原特异性CD 8 + T细胞应答的能力不依赖于NKG 2D配体与NKG 2D受体的相互作用。
The expression of the Adenovirus serotype 2 or serotype 5 (Ad2/5) E1A gene in tumor cells upregulates ligands that are recognized by the NKG2D activating receptor, which is expressed on NK cells and T cells, and reduces their tumorigenicity, a process dependent on NK cells and T cells. In some model systems, the forced overexpression of NKG2D ligands on tumor cells induced antigen-specific CD8+ T cells that mediated anti-tumor immunity. We wanted to determine if the interaction of NKG2D ligands on tumor cells that express E1A with NKG2D on immune cells contributed to the ability of E1A to induce a CD8+ T cell anti-tumor response or reduce tumorigenicity. To address these questions, we used the MCA-205 tumor cell line or MCA-205 cells that expressed Ad5 E1A (MCA-205-E1A cells), a fusion protein of E1A and ovalbumin (MCA-205-E1A-OVA) or OVA (MCA-205-OVA). We found that the expression of E1A or E1A–OVA, but not OVA, upregulated the expression of the NKG2D ligand RAE-1 on the surface of MCA-205 cells. Additionally, MCA-205-E1A cells and MCA-205-E1A-OVA cells were more sensitive to NK cell lysis than MCA-205 or MCA-205-OVA cells in WT B6 mice, but not NKG2D deficient B6 mice. Next, we adoptively transferred WT or NKG2D deficient OT-1 T cells (CD8 T cells that recognize OVA residues 257–264) into WT B6 mice or B6 mice that were deficient in NKG2D respectively and measured the expansion of OT-1 cells following immunization with MCA-205-E1A-OVA or MCA-205-OVA cells. We found that the expansion of OT-1 cells following immunization of either OVA-expressing MCA-205 cell lines was not affected by the presence or absence of NKG2D in B6 mice. Finally, we found that the capacity of E1A to reduce the tumorigenicity of MCA-205 cells was not impaired in B6-NKG2D deficient mice as compared to WT B6 mice. Our results suggest that the ability of E1A to reduce the tumorigenicity of MCA-205 cells, or induce an antigen-specific CD8+ T cell response, is independent of the interaction of NKG2D ligands with the NKG2D receptor.