Regulation of CD1D expression by murine tumor cells: Escape from immunosurveillance or alternate target molecules?
Regulation of CD1D expression by murine tumor cells: Escape from immunosurveillance or alternate target molecules?
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DOI：
10.1002/ijc.10141
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发表时间：
2002-03-20
影响因子：
6.4
通讯作者：
Maeurer, MJ
中科院分区：
文献类型：
--
作者：
Fiedler, T;Walter, W;Maeurer, MJ
Alphata + TCR T 细胞识别 MHC I 类或 II 类分子展示的肽片段。最近，T 细胞识别抗原的其他机制已被确定，包括 CD1 介导的非肽抗原呈递。小鼠体内仅保留有限数量的 CD1 抗原，即 II 类 CD1 抗原，分为 CD1d1 和 CD1d2。一些 T 细胞亚群已被证明与鼠 CD1 抗原相互作用，包括 NK 细胞或具有不变的 Valpha14 Jalpha281 TCR 链的“天然 T 细胞”。即使 TAP 缺陷可能会阻止肿瘤细胞系中经典的内源性抗原呈递，但通过 CD1 的抗原呈递仍然具有功能。因此，CD1 介导的 NK 细胞或“天然 T 细胞”对转化细胞的识别可能代表了免疫监视的另一种方式。不同组织学的小鼠肿瘤细胞系，包括B细胞淋巴瘤A20、巨噬细胞系J774和P388D1、肥大细胞瘤P815、胸腺瘤EL-4、黑色素瘤B 16、结肠腺癌MC-38和肾癌Renca中CD1细胞表面表达受Th1-(IFN-gamma)、Th2-(IL-4、 IL-10 和 vIL-10) 或 GM-CSF (Th1/Th2) 细胞因子，具体取决于肿瘤组织学。为了区分 CD1d1 和 CD1d2 分子，我们通过比率 RT-PCR 检查了这些 CD1 亚型的差异表达：A20、EL-4、P815 和 MC-38 细胞仅表达 CD1D1 转录物，但不表达 CD1D2 mRNA，与细胞因子处理无关。 CD1d 表达减少导致新鲜分离的 NIK1.1(+) 效应细胞对 CD1d+ 肿瘤细胞的免疫识别减少，如细胞溶解和 IFN-γ 释放所定义。因此，通过细胞因子调节肿瘤细胞上的 CD1 表达可能有利于驱动针对 TAP 独立的非经典 MHC 限制分子的细胞抗肿瘤抗原定向免疫反应。 (C) 2002 Wiley-Liss, Inc.
alphabeta + TCR T cells recognize peptide fragments displayed by MHC-class I or -class II molecules. Recently, additional mechanisms of antigen recognition by T cells have been identified, including CD1-mediated presentation of nonpeptide antigens. Only a limited number of CD1 antigens is retained in the mouse, i.e., the group II CD1 antigens, which are split into CD1d1 and CD1d2. Several T cell subsets have been shown to interact with murine CD1 antigens, including NK cells or "natural T cells" with the invariant Valpha14 Jalpha281 TCR chain. Even if TAP defects may prevent classical endogenous antigen presentation in tumor cell lines, antigen presentation via CD1 is still functional. Therefore, CD1-mediated recognition of transformed cells by NK cells or "natural T cells" may represent an alternative way for immune surveillance. CD1 cell surface expression in murine tumor cell lines of different histology, including the B cell lymphoma A20, macrophage cell lines J774 and P388D1, mastocytoma P815, thymoma EL-4, melanoma B 16, colon adenocarcinoma MC-38 and renal carcinoma Renca is regulated by Th1 - (IFN-gamma), Th2- (IL-4, IL-10 and vIL-10) or GM-CSF (Th1/Th2) cytokines, depending on the tumor histology. In order to distinguish between CD1d1 and CD1d2 molecules, we examined differential expression of these CD1 isoforms by ratio RT-PCR: A20, EL-4, P815 and MC-38 cells exclusively express CD1D1 transcripts but not CD1D2 mRNA independent of cytokine treatment. Decreased CD1d expression leads to reduced immune recognition of CD1d+ tumor cells by freshly isolated NIK1.1(+) effector cells as defined by cytolysis and IFN-gamma release. Thus, modulation of CD1 expression on tumor cells by cytokines may be advantageous to drive cellular antitumor antigen directed immune responses directed against TAP-independent, non-classical MHC restricting molecules. (C) 2002 Wiley-Liss, Inc.