T-CELL SUBSETS REQUIRED FOR INTRAVESICAL BCG IMMUNOTHERAPY FOR BLADDER-CANCER
T-CELL SUBSETS REQUIRED FOR INTRAVESICAL BCG IMMUNOTHERAPY FOR BLADDER-CANCER
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DOI：
10.1016/s0022-5347(17)35678-1
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发表时间：
1993-09-01
影响因子：
6.6
通讯作者：
CATALONA, WJ
中科院分区：
文献类型：
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作者：
RATLIFF, TL;RITCHEY, JK;CATALONA, WJ
膀胱灌注卡介苗（BCG）已在前瞻性随机临床试验中显示为浅表性膀胱癌的首选治疗。在这项研究中，我们评估了CD 4和CD 8淋巴细胞在抗肿瘤反应中的作用。静脉内注射抗Thy 1.2、CD 8、CD 4的单克隆抗体和同种型对照以消耗T细胞群。耗尽后（通过流式细胞术验证），开始BCG治疗。结果表明，CD 4或CD 8 T细胞亚群的耗竭消除了BCG介导的抗肿瘤活性。脚垫迟发型超敏反应（DTH）流产，只有在CD 4耗竭小鼠，它是基本上没有变化的CD 8耗竭小鼠。然而，DTH的存在不足以诱导BCG介导的抗肿瘤活性。外源性IL-2在足以诱导淋巴因子激活的杀伤细胞活性的水平下不能替代CD 4细胞。没有证据表明BCG治疗后诱导了对肿瘤的保护性免疫。这些结果表明BCG介导的抗肿瘤活性需要T淋巴细胞，并进一步证明需要CD 4和CD 8亚群的存在。CD 8耗竭实验表明，CD 4介导的DTH的存在不足以诱导抗肿瘤活性。此外，这些数据表明BCG介导的抗肿瘤活性是一种局部现象，不会诱导保护性免疫。
Intravesical bacille Calmette-Guerin (BCG) has been shown in prospective randomized clinical trials to be the treatment of choice for superficial bladder cancer. In this investigation we evaluated the role of CD4 and CD8 lymphocytes in the antitumor response. Monoclonal antibodies to thy 1.2, CD8, CD4 and an isotype control were injected intravenously to deplete T cell populations. After depletion (verified by flow cytometry), BCG therapy was initiated. The results demonstrate that the depletion of either CD4 or CD8 T cell subsets eliminated BCG-mediated antitumor activity. Footpad delayed type hypersensitivity (DTH) was aborted only in CD4 depleted mice; it was essentially unchanged in CD8 depleted mice. However, the presence of DTH was not sufficient for induction of BCG-mediated antitumor activity. Exogenous IL-2 at levels sufficient to induce lymphokine activated killer cell activity did not substitute for CD4 cells. There was no evidence for the induction of protective immunity to the tumor after BCG therapy. These results demonstrate the requirement for T lymphocytes in BCG-mediated antitumor activity and further demonstrate that the presence of both CD4 and CD8 subsets are required. CD8 depletion experiments suggest that the presence of CD4-mediated DTH is not sufficient for the induction of antitumor activity. Furthermore, these data suggest that BCG-mediated antitumor activity is a localized phenomenon that does not induce protective immunity.