Enhanced expansion of the thymic CD8+ cell subset as a potential mechanism for the generation of enhanced antitumor cytotoxicity by thymocytes from low-dose melphalan-treated MOPC-315 tumor bearers.
Enhanced expansion of the thymic CD8+ cell subset as a potential mechanism for the generation of enhanced antitumor cytotoxicity by thymocytes from low-dose melphalan-treated MOPC-315 tumor bearers.
复制标题
胸腺 CD8 细胞亚群的增强扩增是低剂量美法仑处理的 MOPC-315 肿瘤携带者胸腺细胞产生增强抗肿瘤细胞毒性的潜在机制。
DOI：
10.1007/bf01741340
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Mokyr,MB
中科院分区：
文献类型：
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作者：
Bartik,MM;Baumgartel-Scofield,BA;Mokyr,MB
我们之前已经证明低剂量美法仑的胸腺细胞（l-苯丙氨酸氮芥）处理的MOPC-315荷瘤小鼠（美法仑TuB）能够产生增强水平的抗MOPC-315细胞毒性，与来自未处理的MOPC-315荷瘤小鼠的胸腺细胞或来自未处理或低剂量美法仑处理的正常小鼠的胸腺细胞相比，在低浓度重组白细胞介素-2（rIL-2）存在下，用MOPC-315肿瘤细胞体外刺激后。在这里，我们表明，产生增强的抗MOPC-315细胞毒性的美法仑TuB胸腺细胞依赖于胸腺细胞增殖的能力。此外，美法仑TuB胸腺细胞产生增强水平的抗MOPC-315细胞毒性的能力与其比来自未处理的荷瘤小鼠的胸腺细胞和来自未处理或美法仑处理的正常小鼠的胸腺细胞响应于MOPC-315肿瘤细胞加低浓度rIL-2的刺激更容易增殖的能力相关。此外，尽管新鲜的美法仑TuB胸腺细胞不含有较高百分比的表型成熟细胞（即，在用MOPC-315肿瘤细胞和低浓度rIL-2培养5天后，来自美法仑TuB的胸腺细胞培养物含有比来自其他两种来源的胸腺细胞培养物高得多的CD 4 −/CD 8+（但不是CD 4 +/CD 8 −）细胞百分比。由于CD 4 −/CD 8+细胞先前被证明是MOPC-315体外刺激的胸腺细胞发挥抗肿瘤细胞毒性的原因，我们的结果表明，在低浓度rIL-2存在下，MOPC-315肿瘤细胞体外刺激后，美法仑TuB胸腺细胞发挥的增强的抗肿瘤细胞毒性至少部分是由于，CD 4 −/CD 8+效应细胞库的扩增。
We have previously shown that thymocytes from low-dose melphalan (l-phenylalanine mustard)-treated MOPC-315-tumor-bearing mice (melphalan TuB) are able to generate an enhanced level of anti-MOPC-315 cytotoxicity, as compared to thymocytes from untreated MOPC-315-tumor-bearing mice or thymocytes from untreated or low-dose melphalan-treated normal mice, upon in vitro stimulation with MOPC-315 tumor cells in the presence of a low concentration of recombinant interleukin-2 (rIL-2). Here we show that the generation of enhanced anti-MOPC-315 cytotoxicity by melphalan TuB thymocytes depends on the ability of the thymocytes to proliferate. In addition, the ability of melphalan TuB thymocytes to generate an enhanced level of anti-MOPC-315 cytotoxicity correlated with their ability to proliferate more readily than thymocytes from untreated tumor-bearing mice and thymocytes from untreated or melphalan-treated normal mice in response to stimulation with MOPC-315 tumor cells plus a low concentration of rIL-2. Moreover, although fresh melphalan TuB thymocytes do not contain a higher percentage of phenotypically mature cells (i.e., CD4−/CD8+or CD4+/CD8−) than do thymocytes from normal mice or untreated tumor-bearing mice, after a 5-day culture with both MOPC-315 tumor cells and a low concentration of rIL-2, cultures of thymocytes from melphalan TuB contained a much higher percentage of CD4−/CD8+(but not CD4+/CD8−) cells than did cultures of thymocytes from the other two sources. Since CD4−/CD8+cells were previously shown to be responsible for the exertion of antitumor cytotoxicity by thymocytes stimulated with MOPC-315 in vitro, our results indicate that the enhanced antitumor cytotoxicity exerted by melphalan TuB thymocytes following in vitro stimulation with MOPC-315 tumor cells in the presence of a low concentration of rIL-2 is due, at least in part, to an expansion of the pool of CD4−/CD8+effector cells.