Interleukin 10 pretreatment protects target cells from tumor- and allo-specific cytotoxic T cells and downregulates HLA class I expression.
Interleukin 10 pretreatment protects target cells from tumor- and allo-specific cytotoxic T cells and downregulates HLA class I expression.
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DOI：
10.1084/jem.180.6.2371
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发表时间：
1994-12-01
期刊：
影响因子：
--
通讯作者：
Kiessling R
中科院分区：
文献类型：
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作者：
Matsuda M;Salazar F;Petersson M;Masucci G;Hansson J;Pisa P;Zhang QJ;Masucci MG;Kiessling R
白细胞介素10（IL-10）是一种细胞因子，具有多种报道的作用，包括抑制单核细胞主要组织相容性复合物（MHC）II类依赖性抗原呈递、1型辅助T细胞细胞因子产生和抑制T细胞增殖。在此，我们报告了IL-10预处理对抗原呈递给肿瘤和同种异体特异性CD 8+细胞毒性T淋巴细胞（CTL）的影响。将人黑素瘤细胞与重组IL-10（rIL-10）预先孵育48-72小时导致自体CTL介导的HLA-A2.1限制性肿瘤特异性裂解的剂量依赖性抑制，高达100%。同种特异性CTL对EB病毒转化的淋巴母细胞系（LCL）的细胞毒性也被抑制，表明对淋巴样细胞也有保护作用。相比之下，IL-10预处理同种异体LCL或K562靶点对新鲜分离的或IL-2激活的自然杀伤细胞介导的细胞毒活性没有影响或略有增强。用抗HLA-A2或MHC I类蛋白非多态性决定簇的单克隆抗体进行流式细胞术分析，发现细胞表面表达减少20-50%，而细胞间粘附分子1和2以及淋巴细胞功能相关抗原3水平不受影响。此外，相对于未处理的靶细胞，IL-10预处理的肿瘤细胞通过冷靶抑制影响CTL介导的裂解的能力没有改变，表明IL-10的作用与CTL与其靶的初始结合无关。这些结果与IL-10对MHC I类抗原呈递途径的作用相一致，并提示了基于从CTL介导的肿瘤和同种异体移植排斥中逃逸的免疫耐受的新机制。
Interleukin 10 (IL-10) is a cytokine with a variety of reported effects including inhibition of monocyte major histocompatibility complex (MHC) class II-dependent antigen presentation, type 1 helper T cell cytokine production, and inhibition of T cell proliferation. Herein we report the effect of IL-10 pretreatment on antigen presentation to tumor- and allo-specific CD8+ cytotoxic T lymphocytes (CTL). Prior incubation of human melanoma cells with recombinant IL-10 (rIL-10) for 48-72 h resulted in a dose-dependent, up to 100% inhibition, of autologous CTL- mediated, HLA-A2.1-restricted, tumor-specific lysis. Allo-specific CTL cytotoxicity against Epstein-Barr virus-transformed lymphoblastoid cell lines (LCL) was also inhibited, demonstrating a protective effect also on lymphoid cells. In contrast, IL-10 pretreatment of allogeneic LCL or K562 targets had either no effect or slightly enhanced cytotoxic activity mediated by freshly isolated or IL-2-activated natural killer cells. Flow cytometric analysis with monoclonal antibodies against HLA- A2, or nonpolymorphic determinants of MHC class I proteins, revealed a 20-50% reduction in cell-surface expression, whereas intercellular adhesion molecules 1, and 2, and lymphocyte function-associated antigen 3 levels were not affected. In addition, relative to untreated target cells, IL-10 pretreated tumor cells were unaltered in their capacity to affect CTL-mediated lysis by cold target inhibition, demonstrating that the effect of IL-10 is unrelated to the initial binding of CTL to their targets. These results are compatible with an effect of IL-10 on the MHC class I antigen presentation pathway, and suggest a novel mechanism of immune tolerance, based on escape from CTL-mediated tumor and allo- transplant rejection.