Immunologically mediated regression of a murine lymphoma after treatment with anti-L3T4 antibody. A consequence of removing L3T4+ suppressor T cells from a host generating predominantly Lyt-2+ T cell-mediated immunity.
Immunologically mediated regression of a murine lymphoma after treatment with anti-L3T4 antibody. A consequence of removing L3T4+ suppressor T cells from a host generating predominantly Lyt-2+ T cell-mediated immunity.
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用抗L3T4抗体治疗后鼠淋巴瘤的免疫学介导的回归。从产生主要是Lyt-2+ T细胞介导的免疫力的宿主中去除L3T4+抑制T细胞的结果。
DOI：
10.1084/jem.168.6.2193
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发表时间：
1988-12-01
期刊：
影响因子：
--
通讯作者：
North RJ
中科院分区：
文献类型：
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作者：
Awwad M;North RJ
本研究表明，静脉注射1mg抗l3t4单抗（GK1.5）给患有同基因L5178Y淋巴瘤的胸腺去切小鼠，延迟2-3天后，肿瘤完全消退，宿主长期存活。对单克隆抗体处理小鼠的脾脏细胞进行的流式细胞荧光检查显示，抗体处理导致超过98%的L3T4+ T细胞被消除，但对Lyt-2+ T细胞亚群没有影响。肿瘤消退是免疫介导的，因为L5178Y淋巴瘤细胞被证明是L3T4-，并且在给予抗L3T4单抗之前被致命照射的小鼠中，肿瘤未能发生消退。肿瘤消退是由肿瘤致敏的Lyt2+ T细胞介导的，研究发现，单独使用抗lyt -2单抗或联合使用抗l3t4单抗治疗荷瘤小鼠，可促进肿瘤生长，显著缩短宿主生存时间。此外，肿瘤因抗l3t4单抗治疗而消退的小鼠脾脏中含有Lyt-2+ T细胞，通过被动转移，能够引起受体小鼠肿瘤消退。这些结果可以解释为，去除肿瘤诱导的L3T4+抑制T细胞导致Lyt-2+效应T细胞从抑制中释放出来，从而产生足够的Lyt-2+ T细胞介导的免疫，从而导致肿瘤消退。然而，这只有在对肿瘤的免疫完全由Lyt-2+ T细胞介导的情况下才能实现，就像L5178Y淋巴瘤一样。在P815肥大细胞瘤的病例中，用抗L3T4单抗治疗没有治疗效果，这与对这种肿瘤的免疫是由L3T4+和Lyt-2+ T细胞介导的发现一致。
This study shows that intravenous injection of 1 mg of anti-L3T4 mAb (GK1.5) into thymectomized mice bearing the syngeneic L5178Y lymphoma results, after a delay of 2-3 d, in complete regression of this tumor and in long-term host survival. A flow cytofluorometric examination of the spleen cells of mAb-treated mice revealed that antibody treatment resulted in the elimination of greater than 98% of L3T4+ T cells, but had no effect on the Lyt-2+ T cells subset. Tumor regression was immunologically mediated, because L5178Y lymphoma cells were shown to be L3T4-, and regression of the tumor failed to occur in mice that had been lethally irradiated before anti-L3T4 mAb was given. Tumor regression was mediated by tumor-sensitized Lyt2+ T cells, as evidenced by the finding that treatment of tumor-bearing mice with anti-Lyt-2 mAb alone, or in combination with anti-L3T4 mAb, resulted in enhancement of tumor growth and a significant decrease in host survival time. Moreover, the spleens of mice whose tumors were undergoing regression in response to anti-L3T4 mAb treatment contained Lyt-2+ T cells capable, on passive transfer, of causing regression of a tumor in recipient mice. These results can be interpreted as showing that removal of tumor-induced L3T4+ suppressor T cells results in the release of Lyt-2+ effector T cells from suppression, and consequently in the generation of enough Lyt-2+ T cell-mediated immunity to cause tumor regression. This can only be achieved, however, if immunity to the tumor is mediated exclusively by Lyt-2+ T cells, as is the case for the L5178Y lymphoma. In the case of the P815 mastocytoma, treatment with anti-L3T4 mAb was without a therapeutic effect, and this was in keeping with the finding that immunity to this tumor is mediated by L3T4+, as well by Lyt-2+ T cells.