Matuszyk J, Kobzdej M, Ziolo E, Kalas W, Kisielow P, Strzadala L
Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Biochem Biophys Res Commun. 1998 Aug 10;249(1):279-82. doi: 10.1006/bbrc.1998.9131.
We reported previously that thymic lymphomas from mice expressing transgenic TCR autoreactive against male (HY) antigen were resistant to anti-CD3 antibody-mediated induction of apoptosis although they were responding to TCR triggering. To test whether thymic lymphomas were specifically resistant to TCR-dependent Ca(++)-mediated induction of apoptosis, we have measured apoptosis of cells treated with Ca(++)-dependent (ionomycin, A23187) and Ca(++)-independent (etoposide, dexamethasone) inducers of apoptosis. Here we show that, unlike thymocytes, all thymic lymphomas were resistant to Ca(++)-dependent but not to Ca(++)-independent induction of apoptosis. These results excluded a general defect of apoptosis in lymphoma cells and suggested a specific inhibition of the calcium-mediated (TCR-dependent) pathway of apoptosis in lymphomas. Interestingly however, nuclear expression of a specific mediator of TCR-dependent apoptosis Nur77 was induced in ionomycin-resistant lymphomas indicating that, unlike normal thymocytes, thymic lymphomas are resistant to Nur77-mediated apoptosis.
我们之前报道过，表达针对雄性（HY）抗原的转基因自身反应性TCR的小鼠胸腺淋巴瘤，尽管对TCR触发有反应，但对抗CD3抗体介导的细胞凋亡诱导具有抗性。为了测试胸腺淋巴瘤是否对TCR依赖性Ca(++)介导的细胞凋亡诱导具有特异性抗性，我们测量了用Ca(++)依赖性（离子霉素、A23187）和Ca(++)非依赖性（依托泊苷、地塞米松）细胞凋亡诱导剂处理的细胞的凋亡情况。在这里我们表明，与胸腺细胞不同，所有胸腺淋巴瘤对Ca(++)依赖性但不对Ca(++)非依赖性细胞凋亡诱导具有抗性。这些结果排除了淋巴瘤细胞中细胞凋亡的普遍缺陷，并提示淋巴瘤中钙介导的（TCR依赖性）细胞凋亡途径受到特异性抑制。然而，有趣的是，在对离子霉素耐药的淋巴瘤中诱导了TCR依赖性细胞凋亡的特异性介质Nur77的核表达，这表明与正常胸腺细胞不同，胸腺淋巴瘤对Nur77介导的细胞凋亡具有抗性。
