细胞毒性T细胞
生物
过继性细胞移植
CD8型
颗粒酶B
免疫学
免疫疗法
白细胞介素2受体
白细胞介素21
颗粒酶
颗粒酶A
T细胞
细胞生物学
免疫系统
抗原
穿孔素
体外
生物化学
作者
Christian S. Hinrichs,Rosanne Spolski,Chrystal M. Paulos,Luca Gattinoni,Keith W. Kerstann,Douglas C. Palmer,Christopher A. Klebanoff,Steven A. Rosenberg,Warren J. Leonard,Nicholas P. Restifo
出处
期刊:Blood
[American Society of Hematology]
日期:2008-06-01
卷期号:111 (11): 5326-5333
被引量:394
标识
DOI:10.1182/blood-2007-09-113050
摘要
IL-2 and IL-21 are closely related cytokines that might have arisen by gene duplication. Both cytokines promote the function of effector CD8(+) T cells, but their distinct effects on antigen-driven differentiation of naive CD8(+) T cells into effector CD8(+) T cells are not clearly understood. We found that antigen-induced expression of Eomesodermin (Eomes) and maturation of naive CD8(+) T cells into granzyme B- and CD44-expressing effector CD8(+) T cells was enhanced by IL-2, but, unexpectedly, suppressed by IL-21. Furthermore, IL-21 repressed expression of IL-2Ra and inhibited IL-2-mediated acquisition of a cytolytic CD8(+) T-cell phenotype. Despite its inhibitory effects, IL-21 did not induce anergy, but instead potently enhanced the capacity of cells to mediate tumor regression upon adoptive transfer. In contrast, IL-2 impaired the subsequent antitumor function of transferred cells. Gene expression studies revealed a distinct IL-21 program that was characterized phenotypically by increased expression of L-selectin and functionally by enhanced antitumor immunity that was not reversed by secondary in vitro stimulation with antigen and IL-2. Thus, the efficacy of CD8(+) T cells for adoptive immunotherapy can be influenced by opposing differentiation programs conferred by IL-2 and IL-21, a finding with important implications for the development of cellular cancer therapies.
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