Lin Syh-Jae, Cheng Po-Jen, Hsiao Shiu-Shan, Lin Hui-Hao, Hung Pei-Fen, Kuo Ming-Ling
Division of Asthma, Allergy, and Rheumatology, Department of Pediatrics, Chang Gung Children's Hospital, Taoyuan, Taiwan.
Am J Hematol. 2005 Oct;80(2):106-12. doi: 10.1002/ajh.20431.
Cytokine immunotherapy using interleukin (IL)-2 and IL-15 may be beneficial for patients receiving umbilical cord blood (CB) transplantation by ameliorating post-transplant T-cell apoptosis. The present study compares the differential effect of IL-15 and IL-2 on survival of phytohemagglutinin (PHA)-activated CB and adult peripheral blood (APB) T lymphocytes. In comparison with IL-2, IL-15 preferentially enhanced the survival of CB PHA-activated T cells by decreasing the caspase-3+ population and by increasing the Bcl-2+ population. Activated CB T cells were more susceptible to TNF-alpha-induced apoptosis compared to their adult counterparts. However, the susceptibility could be abrogated by IL-15 but not by IL-2. IL-15 but not IL-2 down-regulated CD28 expression on both activated CB and APB CD8+ T cells, with a much greater effect seen with CB. Western-blot analysis shows that IL-15 Ralpha is deficient in CB compared to APB immediately after PHA stimulation, while culturing with IL-15 significantly enhanced CB IL-15 Ralpha expression to levels comparable to that of adults. Thus, IL-15 may provide a better therapeutic choice for immune reconstitution than IL-2 post-CB transplantation due to its preferential survival enhancing effect on CB T cells.
使用白细胞介素（IL）-2和IL-15进行细胞因子免疫疗法，可能通过改善移植后T细胞凋亡，对接受脐带血（CB）移植的患者有益。本研究比较了IL-15和IL-2对植物血凝素（PHA）激活的CB和成人外周血（APB）T淋巴细胞存活的不同影响。与IL-2相比，IL-15通过减少caspase-3 +细胞群和增加Bcl-2 +细胞群，优先提高了CB PHA激活的T细胞的存活率。与成人来源的T细胞相比，激活的CB T细胞对TNF-α诱导的凋亡更敏感。然而，这种敏感性可以被IL-15消除，而不能被IL-2消除。IL-15而非IL-2下调了激活的CB和APB CD8 + T细胞上的CD28表达，CB细胞上的这种作用更为明显。蛋白质免疫印迹分析表明，与PHA刺激后立即检测的APB相比，CB中的IL-15 Rα缺乏，而与IL-15一起培养可显著提高CB的IL-15 Rα表达，使其达到与成人相当的水平。因此，由于IL-15对CB T细胞具有优先的存活增强作用，在CB移植后，IL-15可能比IL-2为免疫重建提供更好的治疗选择。
