Class II-transfected tumor cells directly present endogenous antigen to CD4+ T cells in vitro and are APCs for tumor-encoded antigens in vivo
Class II-transfected tumor cells directly present endogenous antigen to CD4+ T cells in vitro and are APCs for tumor-encoded antigens in vivo
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DOI：
10.1097/00002371-199805000-00008
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发表时间：
1998-05-01
影响因子：
3.9
通讯作者：
Ostrand-Rosenberg, S
中科院分区：
文献类型：
--
作者：
Armstrong, TD;Clements, VK;Ostrand-Rosenberg, S
我们先前已经证明，转染了II类分子的肿瘤细胞是非常有效的免疫原，可预防野生型原发性和转移性肿瘤，并且如果再转染编码共刺激分子的基因，它们就成为免疫治疗剂，能够成功治疗患有实体瘤的小鼠。这些结果与我们的假设相符，即转染了II类分子的肿瘤细胞作为抗原呈递细胞（APCs）直接激活肿瘤特异性CD4(+) T细胞；然而，缺乏支持这一假设的直接数据。在本研究中，我们使用转染了II类分子且再转染鸡卵溶菌酶基因作为替代肿瘤抗原的肿瘤细胞来检验这一假设。体外抗原呈递实验表明，转染了II类分子的肿瘤细胞可向内源性编码肿瘤抗原的CD4(+) T细胞呈递抗原，前提是它们不共表达II类分子相关的恒定链。使用基因标记的肿瘤细胞和宿主抗原呈递细胞进行的体内实验表明，转染了II类分子的肿瘤细胞和宿主细胞都是肿瘤编码抗原的抗原呈递细胞，尽管肿瘤细胞似乎在反应中占主导地位。这些结果支持这样的假设：转染了II类分子的肿瘤细胞的免疫原性和治疗价值源于它们作为肿瘤编码抗原的抗原呈递细胞并直接激活肿瘤特异性CD4(+) T淋巴细胞的能力。
We have previously demonstrated that class II-transfected tumor cells are very effective immunogens that protect against wild-type primary and metastatic tumor and, if supertransfected with genes encoding co-stimulatory molecules, are immunotherapeutic agents that successfully treat mice with established solid tumor. These results are consistent with our hypothesis that the class II-transfected tumor cells act as antigen-presenting cells (APCs) that directly activate tumor-specific CD4(+) T cells; however, direct data supporting this hypothesis are lacking. In the present study, we test this hypothesis using class II-transfected tumor cells supertransfected with the hen egg lysozyme gene as a surrogate turner antigen. In vitro antigen presentation assays demonstrate that class II-transfected tumor cells present to CD4(+) T cells endogenously encoded tumor antigen, provided they do not co-express the class II-associated invariant chain. In vivo experiments using genetically marked tumor cells and host APCs demonstrate that both class II-transfected tumor cells and host cells are APCs for tumor-encoded antigens, although tumor cells appear to dominate the response. These results support the hypothesis that the immunogenicity and therapeutic value of class II-transfected tumor cells stem from their ability to function as APCs for tumor-encoded antigens and directly activate tumor-specific CD4(+) T lymphocytes.