Foreman K E, Wrone-Smith T, Krueger A E, Nickoloff B J
Department of Pathology, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, Illinois 60153-5385, USA.
Clin Immunol. 1999 Jun;91(3):345-53. doi: 10.1006/clim.1999.4712.
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.
在静息T细胞的生理刺激过程中,抗原呈递细胞至少需要提供两个激活信号。除了第一个抗原特异性信号外,第二个共刺激信号涉及抗原呈递细胞表达的CD80和CD86。这些共刺激分子在许多不同的自身免疫和恶性疾病过程中被认为具有临床相关性。我们之前观察到,卡波西肉瘤(一种常见的与艾滋病相关的皮肤肿瘤)中的肿瘤细胞完全缺乏CD80和CD86,并且这些肿瘤细胞无法刺激T细胞增殖。在本研究中,使用一种名为SLK的卡波西肉瘤肿瘤细胞系,构建了各种稳定转染的细胞系。对单独表达CD80或CD86的肿瘤细胞以及双阳性细胞系诱导T细胞激活、T细胞增殖和细胞因子产生谱的能力进行了检测。与亲本双阴性肿瘤细胞系相比,CD80阳性细胞而非CD86阳性肿瘤细胞可诱导显著的T细胞激活和增殖。同时表达CD80和CD86的肿瘤细胞也可诱导T细胞激活。经转染的肿瘤细胞刺激后,T细胞产生Th-1型细胞因子产生谱,白细胞介素-2和干扰素-γ水平升高。这些结果表明,缺乏共刺激分子的卡波西肉瘤肿瘤细胞不能诱导T细胞激活;然而,如果它们表达CD80,则可以诱导外周血T细胞增殖,并且由于CD86的表达没有相同的免疫刺激作用,存在差异反应。