Ozdemir Oner, Savaşan Süreyya
Children's Hospital of Michigan, Division of Hematology/Oncology, Wayne State University, Detroit, MI 48201, USA.
Clin Immunol. 2005 Jun;115(3):240-9. doi: 10.1016/j.clim.2005.01.008.
In vitro comparisons of induction of perforin (PFP), granzyme B (GRB), production of cytokines, and cell-mediated cytotoxicity by interleukin-2 (IL-2), interleukin-15 (IL-15), or combinational IL-2/IL-15-induced lymphokine-activated killer cells were studied in this study. Whereas IL-2-induction was associated with a decrease in cultured cell population over a 7-day period, IL-15 alone or in combination with IL-2 resulted in significant increase including cytotoxic T lymphocytes and subsets of CD56+ lymphocytes, particularly cytokine-induced killer and cytolytic natural killer-T lymphocytes. The overall PFP, GRB, and tumor necrosis factor-alpha expression in different subtypes were also significantly higher with IL-15 alone or in combination with IL-2 induction with resultant superior cytotoxicity compared to IL-2 treatment. There was no significant advantage of addition of IL-2 over IL-15 induction. These results offer further information on the cytotoxic potency of these cytokines and their mechanisms of action implicating potential use of IL-15 as part of cytokine adoptive immunotherapy.
本研究对白细胞介素-2(IL-2)、白细胞介素-15(IL-15)或联合使用IL-2/IL-15诱导的淋巴因子激活的杀伤细胞诱导穿孔素(PFP)、颗粒酶B(GRB)、细胞因子产生以及细胞介导的细胞毒性进行了体外比较。在7天的时间里,IL-2诱导与培养细胞数量的减少有关,而单独使用IL-15或与IL-2联合使用则导致显著增加,包括细胞毒性T淋巴细胞和CD56+淋巴细胞亚群,特别是细胞因子诱导的杀伤细胞和溶细胞性自然杀伤T淋巴细胞。与IL-2处理相比,单独使用IL-15或与IL-2联合诱导时,不同亚型中的总体PFP、GRB和肿瘤坏死因子-α表达也显著更高,从而产生了更强的细胞毒性。与IL-15诱导相比,添加IL-2没有显著优势。这些结果为这些细胞因子的细胞毒性效力及其作用机制提供了更多信息,提示IL-15作为细胞因子过继性免疫治疗的一部分具有潜在用途。