Nishimatsu H, Takeuchi T, Ueki T, Kajiwara T, Moriyama N, Ishida T, Li B, Kakizoe T, Kitamura T
Department of Urology, University of Tokyo, Faculty of Medicine, Japan.
Cancer Immunol Immunother. 1999 Apr;48(1):56-61. doi: 10.1007/s002620050548.
The CD95/CD95 ligand (CD95L) system plays an important role in the induction of lymphoid apoptosis and has been implicated in the suppression of immune responses. In this system, two murine CD95L-transfected renca clones and a control renca clone transfected only with the vector were implanted into the subcapsule of the left kidney of Balb/c and Balb/c nude mice. Both CD95L-expressing and control renca clones formed macroscopic tumors in all of the Balb/c and Balb/c nude hosts 14 days after implantation. Growth of tumors of murine CD95L-transfected renca cells was significantly better than that of control renca cells in Balb/c mice, while the growth advantage of CD95L transfectants was not observed in Balb/c nude mice. Lymphocytes underwent apoptosis mainly in the periphery of the CD95L-expressing tumors but not in control tumors grown in Balb/c mice, while lymphocytes undergoing apoptosis were not observed in CD95L-expressing tumors or in control tumors grown in Balb/c nude mice. Neutrophilic recruitment was rarely observed in CD95L-expressing or control tumors. CD95L expressed on renca cells possibly suppressed immune responses against renca tumors by inducing apoptosis of the infiltrating lymphocytes. However, CD95L-expressing renca cells did not form tumors in the renal subcapsule of allogeneic C3H/HeJ mice.
CD95/CD95配体(CD95L)系统在诱导淋巴细胞凋亡中起重要作用,并与免疫反应的抑制有关。在该系统中,将两个转染了小鼠CD95L的肾癌细胞(renca)克隆以及仅转染了载体的对照renca克隆植入Balb/c和Balb/c裸鼠左肾的被膜下。植入后14天,表达CD95L的renca克隆和对照renca克隆在所有Balb/c和Balb/c裸鼠宿主体内均形成肉眼可见的肿瘤。在Balb/c小鼠中,转染小鼠CD95L的renca细胞肿瘤的生长明显优于对照renca细胞,而在Balb/c裸鼠中未观察到CD95L转染子的生长优势。淋巴细胞主要在表达CD95L的肿瘤周边发生凋亡,而在Balb/c小鼠中生长的对照肿瘤中未发生凋亡,在Balb/c裸鼠中生长的表达CD95L的肿瘤或对照肿瘤中均未观察到发生凋亡的淋巴细胞。在表达CD95L的肿瘤或对照肿瘤中很少观察到嗜中性粒细胞募集。renca细胞上表达的CD95L可能通过诱导浸润淋巴细胞的凋亡来抑制针对renca肿瘤的免疫反应。然而,表达CD95L的renca细胞在同种异体C3H/HeJ小鼠的肾被膜下未形成肿瘤。