EXPRESSION AND MODULATION OF MAJOR HISTOCOMPATIBILITY ANTIGENS ON MURINE PRIMARY BRAIN-TUMOR INVITRO
EXPRESSION AND MODULATION OF MAJOR HISTOCOMPATIBILITY ANTIGENS ON MURINE PRIMARY BRAIN-TUMOR INVITRO
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DOI：
10.3171/jns.1991.75.6.0922
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发表时间：
1991-12-01
影响因子：
4.1
通讯作者：
SARIS, SC
中科院分区：
文献类型：
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作者：
AKBASAK, A;OLDFIELD, EH;SARIS, SC
激活的细胞毒性淋巴细胞裂解肿瘤细胞需要它们识别与主要组织相容性复合体分子相关的抗原。作者研究了一类和二类主要组织相容性复合体抗原在小鼠脑肿瘤细胞上的组成性表达，以及不同细胞因子和细胞因子组合在体外改变其表达的能力。将小鼠胶质瘤26 （GL26）、胶质瘤261 （GL261）和室管膜母细胞瘤A （EpA）细胞系的细胞置于单层培养中，用α干扰素、γ干扰素、肿瘤坏死因子α、肿瘤坏死因子α加γ干扰素或白细胞介素-2处理48小时。然后通过流式细胞术分析基线和细胞因子改变的主要组织相容性复合物表达。所有细胞系具有相似的主要组织相容性复合体模式，ⅰ类抗原表达低，ⅱ类抗原表达无检测到。α干扰素显著诱导和上调ⅰ类抗原的表达，而对ⅱ类抗原的表达无影响。γ干扰素也刺激I类抗原表达上调，通常使处理细胞的抗I类抗原荧光增加一倍。其对ⅱ类抗原表达的影响更为广泛。在GL26和GL261细胞系中，II类抗原决定因子的表达增加到对照值的12倍和14倍，并且多达75%的未检测到II类抗原组成表达的细胞在γ干扰素启动后表达了该抗原。在γ干扰素中加入肿瘤坏死因子α进一步增加了II类抗原在EpA肿瘤细胞上的表达。单独使用白细胞介素-2和肿瘤坏死因子α对任何细胞系的I类和II类抗原表达均无影响。结论：在体外用一定的细胞因子处理小鼠胶质瘤细胞系后，可诱导并增强ⅰ类和ⅱ类抗原的表达。利用这些细胞系在C57BL/6小鼠体内原位制造原发脑肿瘤，为研究脑肿瘤细胞中主要组织相容性复合物的调节以及检查主要组织相容性复合物上调对脑肿瘤免疫治疗反应的潜在影响提供了一个很好的动物系统。
Lysis of tumor cells by activated cytotoxic lymphocytes requires their recognition of antigens associated with major histocompatibility complex molecules. The authors studied the constitutive expression of Class I and Class II major histocompatibility complex antigens on mouse brain-tumor cells and the capacity of different cytokines and cytokine combinations to alter this expression in vitro. Cells from the murine glioma 26 (GL26), glioma 261 (GL261), and ependymoblastoma A (EpA) cell lines were established in monolayer culture and treated for 48 hours with either alpha interferon, gamma interferon, tumor necrosis factor alpha, tumor necrosis factor alpha plus gamma interferon, or interleukin-2. They were then analyzed by flow cytometry for baseline and cytokine-altered major histocompatibility complex expression.All cell lines had a similar constitutive major histocompatibility complex pattern with low Class I antigen expression and no detectable Class II antigen expression. Alpha interferon substantially induced and up-regulated Class I antigen expression, but had no effect on Class II antigen expression. Gamma interferon also stimulated up-regulation of Class I antigen expression, generally doubling the anti-Class I antigen fluorescence of treated cells. Its effect on Class II antigen expression was more extensive. In the GL26 and GL261 cell lines, the expression of Class II antigen determinants increased to 12 x and 14 x control values and as many as 75% of cells that had no detectable constitutive expression of Class II antigen expressed this antigen after priming with gamma interferon. The addition of tumor necrosis factor alpha to gamma interferon further increased Class II antigen expression on EpA tumor cells only. Interleukin-2 and tumor necrosis factor alpha alone had no effect on Class I or Class II antigen expression of any cell lines.It is concluded that Class I and Class II antigen expression in mouse glioma cell lines is induced and enhanced after treatment with certain cytokines in vitro. Use of these cell lines to create in situ primary brain tumors in C57BL/6 mice should provide an excellent animal system to study major histocompatibility complex modulation in brain tumor cells and to examine the potential impact of major histocompatibility complex up-regulation on the response of brain tumors to immunotherapy.