CD80-transfected human breast and ovarian tumor cell lines: improved immunogenicity and induction of cytolytic CD8+ T lymphocytes.

Cytokines and molecular therapy Pub Date : 1995-09-01
B Gückel, M Lindauer, W Rudy, A Habicht, M Siebels, S Kaul, G Bastert, S C Meuer, U Moebius
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Abstract

Human tumor cell lines derived from breast and ovarian carcinomas have been found to be ineffective in stimulating the induction phase of an immune response such as T cell proliferation in allogeneic mixed tumor cell lymphocyte cultures. Since representative tumor cell lines are effectively lysed by activated T lymphocytes, the induction of an effector phase is not impaired. In order to reconstitute the potential to induce primary T cell activation, we transfected CD80 into a breast (KS) and an ovarian carcinoma (GG) cell line. CD80 expression in KS cells resulted in improved primary T cell activation, whereas it was ineffective in the case of GG cells. However, treatment of CD80-transfected GG cells with INF-gamma rendered them immunogenic, and resulted in T cell proliferation. Likewise, TNF-alpha and/or INF-gamma augmented T cell proliferation induced by CD80-transfected KS cells. Furthermore, T lymphocytes stimulated with cytokine-treated CD80+ KS cells gave rise to a long term proliferating CD8+ CTL line with class I MHC restricted cytolytic antitumor activity. These studies emphasize the requirement for costimulation in generating tumor-specific immunity, and demonstrate the efficacy of CD80 in generating CD8+ cytolytic T lymphocytes.

cd80转染的人乳腺和卵巢肿瘤细胞系:提高免疫原性和诱导细胞溶解性CD8+ T淋巴细胞
来源于乳腺癌和卵巢癌的人类肿瘤细胞系已经被发现在刺激免疫反应的诱导阶段是无效的,例如在异体混合肿瘤细胞淋巴细胞培养中T细胞增殖。由于具有代表性的肿瘤细胞系被活化的T淋巴细胞有效地裂解,效应期的诱导不会受损。为了重建诱导原代T细胞活化的潜力,我们将CD80转染到乳腺癌(KS)和卵巢癌(GG)细胞系中。CD80在KS细胞中的表达可改善原代T细胞的活化,而在GG细胞中则无效。然而,用inf - γ处理cd80转染的GG细胞使它们具有免疫原性,并导致T细胞增殖。同样,tnf - α和/或inf - γ增强了cd80转染的KS细胞诱导的T细胞增殖。此外,细胞因子处理的CD80+ KS细胞刺激T淋巴细胞产生长期增殖的CD8+ CTL系,其I类MHC抑制了细胞溶解抗肿瘤活性。这些研究强调了共刺激在产生肿瘤特异性免疫中的必要性,并证明了CD80在产生CD8+溶细胞T淋巴细胞中的功效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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