Ma D, Niederkorn J Y
Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas 75235-9057, USA.
Immunology. 1995 Oct;86(2):263-9.
Intraocular melanomas, especially those of the anterior segment, reside within an immunologically privileged milieu. Aqueous humour contains a variety of immunomodulatory factors that are believed to contribute to ocular immune privilege. Among these is transforming growth factor-beta (TGF-beta), which has been shown to down-regulate major histocompatibility complex (MHC) class I antigens on normal cells. Since the susceptibility of tumour cells to natural killer (NK) cell-mediated lysis is inversely correlated with the expression of MHC class I antigens, tumour cells exposed to TGF-beta might be expected to experience enhanced susceptibility to NK-mediated killing. This was examined by incubating two human uveal melanoma cell lines in the presence of TGF-beta and evaluating the expression of MHC class I antigen and susceptibility to NK cell-mediated lysis. OCM1 and OCM8 melanoma cells constitutively express high levels of class I antigen (85-90% positive) and low susceptibility to NK-mediated lysis in vitro (3-8%). Incubation with TGF-beta produced a significant reduction in class I antigen expression (52-62%) and a proportional increased susceptibility to NK cell-mediated cytolysis (17%). Analogous effects were found using a human uveal melanoma cell line (OCM3) that constitutively expresses low amounts of class I (< 5% positive) and high NK susceptibility (35% lysis). Stimulation of class I antigen expression by incubation with interferon-gamma resulted in a sharp increase in class I expression (80% positive) and a comparable diminution in susceptibility to NK cell-mediated lysis (< 10%). The results indicate that TGF-beta, at concentrations found in the aqueous humour, can significantly alter MHC class I antigen expression and the susceptibility of ocular melanoma cells to NK cell-mediated cytolysis.
眼内黑色素瘤，尤其是前段的黑色素瘤，存在于免疫赦免环境中。房水含有多种免疫调节因子，据信这些因子有助于眼部免疫赦免。其中包括转化生长因子-β（TGF-β），它已被证明能下调正常细胞上的主要组织相容性复合体（MHC）I类抗原。由于肿瘤细胞对自然杀伤（NK）细胞介导的裂解的敏感性与MHC I类抗原的表达呈负相关，因此暴露于TGF-β的肿瘤细胞可能会增强对NK介导杀伤的敏感性。通过在TGF-β存在的情况下培养两个人类葡萄膜黑色素瘤细胞系，并评估MHC I类抗原的表达和对NK细胞介导裂解的敏感性来对此进行研究。OCM1和OCM8黑色素瘤细胞组成性地表达高水平的I类抗原（85%-90%呈阳性），并且在体外对NK介导的裂解敏感性较低（3%-8%）。与TGF-β一起孵育导致I类抗原表达显著降低（52%-62%），并且对NK细胞介导的细胞溶解的敏感性成比例增加（17%）。使用一个组成性表达少量I类抗原（<5%呈阳性）且对NK敏感性高（35%裂解）的人类葡萄膜黑色素瘤细胞系（OCM3）也发现了类似的效果。通过与干扰素-γ一起孵育刺激I类抗原表达导致I类表达急剧增加（80%呈阳性），并且对NK细胞介导的裂解的敏感性相应降低（<10%）。结果表明，在房水中发现的浓度的TGF-β可显著改变MHC I类抗原表达以及眼内黑色素瘤细胞对NK细胞介导的细胞溶解的敏感性。
