Eradication of disseminated murine leukemia by chemoimmunotherapy with cyclophosphamide and adoptively transferred immune syngeneic Lyt-1+2- lymphocytes.
Eradication of disseminated murine leukemia by chemoimmunotherapy with cyclophosphamide and adoptively transferred immune syngeneic Lyt-1+2- lymphocytes.
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DOI：
10.1084/jem.154.3.952
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发表时间：
1981-09-01
期刊：
影响因子：
--
通讯作者：
Fefer A
中科院分区：
文献类型：
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作者：
Greenberg PD;Cheever MA;Fefer A
测定了在体内对晚期Friend病毒诱导的（FBL）白血病的免疫治疗有效的T细胞表型和体外对FBL的细胞毒性。用环磷酰胺联合过继转移同基因免疫淋巴细胞成功地治疗了播散性FBL白血病小鼠。治疗效果在很大程度上取决于转移细胞中Lyt-1+2- T细胞的存在，而体外对FBL肿瘤具有细胞毒性的细胞来源于Lyt-1+2+和Lyt-1-2+亚群。因此，在过继性化学免疫治疗中根除肿瘤所需的优势细胞在体外对肿瘤不具有细胞溶解性。潜在地，Lyt-1+2-细胞可以在体内作为放大器细胞而不是通过直接的抗肿瘤作用来操作。用α-Lyt-1和补体消除Lyt-1+群体防止了在对同种异体抗原的体外致敏和肿瘤致敏细胞的体外致敏期间产生显著的细胞毒性应答。Lyt-1+细胞耗尽的群体产生细胞毒性应答的能力通过在培养开始时加入白细胞介素2（interleukin 2）而部分重建，白细胞介素2是一种衍生自Lyt-1+2-细胞的T细胞生长因子，其含有CTL和CTL前体，在体外几乎与未分离的免疫细胞一样有效。如果剩余的效应细胞（即，Lyt- 1+2- T细胞）在体内主要作为放大细胞起作用，那么携带肿瘤的宿主必须能够对治疗结果做出积极贡献。
The phenotype of T cells therapeutically effective in immunotherapy of advanced Friend virus-induced (FBL) leukemia in vivo and cytotoxic to FBL in vitro was determined. Mice bearing disseminated FBL leukemia were successfully treated by a combination of cyclophosphamide and adoptive transfer of syngeneic immune lymphocytes. Therapeutic efficacy was largely dependent on the presence of Lyt-1+2- T cells in the transferred cells, whereas cells cytotoxic to FBL tumor in vitro were derived from the Lyt-1+2+ and Lyt-1-2+ subsets. Thus, the predominate cell required to eradicate tumor in adoptive chemoimmunotherapy was not cytolytic to tumor in vitro. Potentially, the Lyt-1+2- cell may operate in vivo as an amplifier cell rather than by a direct anti-tumor effect. Elimination of the Lyt-1+ population with alpha-Lyt-1 and complement prevented the generation of significant cytotoxic responses during both primary in vitro sensitization to alloantigens and in vitro sensitization of tumour-primed cells. The capacity of Lyt-1+ cell- depleted population to generate cytotoxic responses was partially reconstituted by addition, at the initiation of culture, of interluekin 2, a T cell growth factor derived from Lyt-1+2- cells, which contain the CTL and CTL precursors, were nearly as effective in vitro as unseparated immune cells. If the remaining effector cells (i.e., Lyt- 1+2- T cells) function in vivo predominantly as amplifier cells, than the tumour-bearing host must be capable of making a positive contribution to the outcome of therapy.