Dessureault S, Gallinger S
Department of Surgery, Mount Sinai Hospital, Samuel Lunenfeld Research Institute, University of Toronto, Ontario, Canada.
J Surg Res. 1996 Jul 15;64(1):42-8. doi: 10.1006/jsre.1996.0304.
Recent studies suggest that expression of B7-1 by tumor cells is effective at inducing antitumor immune responses. Our purpose was to transfect three human cancer cell lines (MEWO, WM35, and H125) with a B7-1 expression plasmid and test the immunogenicity of these modified cancer cells using allogeneic human peripheral blood lymphocytes (PBLs). PBLs were tested in vitro for both proliferative and cytotoxic activity against parental and B7-transfected tumor cells. [3H]thymidine lymphocyte proliferation assays showed that PBLs incubated with B7-1+ WM35 [major histocompatibility complex (MHC) class I+II+ melanoma] demonstrated a substantial increase in T cell proliferation (P < 0.0005), but PBLs incubated with B7-1+ MEWO (MHC class I-II- melanoma) and H125 (MHC class I+II- lung adenosquamous carcinoma) did not. T-cell-mediated cytotoxicity was not increased against B7-1+ tumor cells: effector T lymphocytes primed against B7-1+ tumor cells did not show any increase in cytolytic activity against 51Cr-labeled B7-1+ or B7-1- target cells. NK cells did not lyse MEWO cells, but they did kill H125 and WM35 targets. B7-1 expression on MEWO and WM35 cells did not result in enhanced lysis by NK cells, but NK cytotoxicity was enhanced by B7-1 expression on H125 cells (P < 0.01). The observation that NK cytotoxicity is enhanced by B7-1+ H125 cells suggests that B7-1/CD28 interactions may be important in NK cytotoxic activity. We conclude that B7-1+ WM35 cells, which express both MHC molecules and antigenic epitopes, elicit an improved alloantigen-induced T cell proliferative response, presumably because they have the capacity to deliver an adequate antigen-specific signal which can be costimulated by B7-1/CD28 interaction.
近期研究表明，肿瘤细胞表达B7-1可有效诱导抗肿瘤免疫反应。我们的目的是用B7-1表达质粒转染三种人类癌细胞系（MEWO、WM35和H125），并使用异体人类外周血淋巴细胞（PBL）检测这些经修饰癌细胞的免疫原性。对PBL进行体外检测，观察其针对亲本肿瘤细胞和B7转染肿瘤细胞的增殖活性和细胞毒性。[3H]胸苷淋巴细胞增殖试验表明，与B7-1+ WM35（主要组织相容性复合体（MHC）I类+II类+黑色素瘤）共同孵育的PBL显示T细胞增殖显著增加（P < 0.0005），但与B7-1+ MEWO（MHC I类-II类-黑色素瘤）和H125（MHC I类+II类-肺腺鳞癌）共同孵育的PBL则未出现这种情况。针对B7-1+肿瘤细胞，T细胞介导的细胞毒性并未增加：针对B7-1+肿瘤细胞致敏的效应T淋巴细胞对51Cr标记的B7-1+或B7-1-靶细胞的溶细胞活性未显示任何增加。NK细胞不能裂解MEWO细胞，但能杀伤H125和WM35靶细胞。MEWO和WM35细胞上的B7-1表达并未导致NK细胞增强裂解作用，但H125细胞上的B7-1表达增强了NK细胞的细胞毒性（P < 0.01）。B7-1+ H125细胞增强NK细胞毒性这一观察结果表明，B7-1/CD28相互作用可能在NK细胞毒性活性中起重要作用。我们得出结论，表达MHC分子和抗原表位的B7-1+ WM35细胞可引发改善的同种异体抗原诱导的T细胞增殖反应，大概是因为它们有能力传递足够的抗原特异性信号，该信号可由B7-1/CD28相互作用进行共刺激。
