Expression of costimulatory molecules CD80 and/or CD86 by a Kaposi's sarcoma tumor cell line induces differential T-cell activation and proliferation.
Expression of costimulatory molecules CD80 and/or CD86 by a Kaposi's sarcoma tumor cell line induces differential T-cell activation and proliferation.
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DOI：
10.1006/clim.1999.4712
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发表时间：
1999-06
影响因子：
8.6
通讯作者：
K. Foreman;T. Wrone-Smith;A. Krueger;B. Nickoloff
中科院分区：
文献类型：
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作者：
K. Foreman;T. Wrone-Smith;A. Krueger;B. Nickoloff
在对静息T细胞的生理刺激过程中，至少需要两个抗原提呈细胞的激活信号。除了第一个抗原特异性信号外，第二个共刺激信号还涉及抗原提呈细胞表达的CD80和CD86。这些共刺激分子被认为在许多不同的自身免疫和恶性疾病过程中具有临床意义。我们此前观察到，Kaposi肉瘤(一种常见的艾滋病相关皮肤肿瘤)中的肿瘤细胞完全缺乏CD80和CD86，这些肿瘤细胞无法刺激T细胞增殖。在本研究中，使用命名为SLK的Kaposi肉瘤细胞系，获得了各种稳定的转基因细胞系。对CD80或CD86单阳性的肿瘤细胞以及双阳性的肿瘤细胞株进行了检测，以了解它们诱导T细胞激活、T细胞增殖和细胞因子产生的能力。与亲代双阴性肿瘤细胞系相比，CD80阳性细胞，而不是CD86阳性肿瘤细胞，诱导了显著的T细胞活化和增殖。同时表达CD80和CD86的肿瘤细胞也能诱导T细胞活化。在转基因肿瘤细胞的刺激下，T细胞产生Th-1型细胞因子，IL-2和干扰素-γ水平升高。这些结果表明，缺乏共刺激分子的Kaposi肉瘤细胞不能诱导T细胞活化，但如果它们表达CD80，它们可以诱导外周血T细胞增殖，并且存在差异，因为CD86的表达没有同样的免疫刺激作用。
During physiological stimulation of resting T-cells, at least two activation signals by antigen presenting cells are required. Besides the first antigen-specific signal, the second costimulatory signal involves CD80 and CD86 expressed by the antigen presenting cell. These costimulatory molecules have been suggested to be of clinical relevance in many different autoimmune and malignant disease processes. We previously observed that tumor cells in Kaposi's sarcoma (a common AIDS-related cutaneous neoplasm) completely lack both CD80 and CD86, and these tumor cells fail to stimulate T-cell proliferation. In this study, using a Kaposi's sarcoma tumor cell line designated SLK, various stable transfected cell lines were produced. Tumor cells that were either singly positive for either CD80 or CD86, as well as a double-positive cell line, were examined for their ability to induce T-cell activation, T-cell proliferation, and cytokine production profiles. Compared to the parental double-negative tumor cell line, the CD80-positive cells, but not the CD86-positive tumor cells, induced significant T-cell activation and proliferation. Tumor cells expressing both CD80 and CD86 also induced T-cell activation. After stimulation by the transfected tumor cells, T-cells produced a Th-1 type cytokine production profile with increased IL-2 and IFN-gamma levels. These results demonstrate that Kaposi's sarcoma tumor cells lacking co-stimulatory molecules cannot induce T-cell activation; however, if they express CD80, they can induce peripheral blood T-cell proliferation, and there is a differential response as expression of CD86 did not have the same immunostimulatory effect.