IL-21 influences the frequency, phenotype, and affinity of the antigen-specific CD8 T cell response
IL-21 influences the frequency, phenotype, and affinity of the antigen-specific CD8 T cell response
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DOI：
10.4049/jimmunol.175.4.2261
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发表时间：
2005-08-15
影响因子：
4.4
通讯作者：
Yee, C
中科院分区：
文献类型：
--
作者：
Li, YQ;Bleakley, M;Yee, C
IL-21是新近发现的一种细胞因子，属于IL-2γ链受体细胞因子家族(包括IL-2、IL-7和IL-15)，被认为是细胞免疫反应的重要调节因子。在这项研究中，IL-21在产生人类抗原特异性CD8(+)T细胞反应中的作用是通过在体外追踪一组罕见但可测量的自身抗原特异性T细胞来表征的。用黑色素瘤抗原识别的T细胞I自体多肽冲击的自体树突状细胞刺激来自人类白细胞抗原A2(+)的健康供者和黑色素瘤患者的CD8(+)T细胞。我们证明，暴露于IL-21可使MART-1特异性CD8(+)T细胞的总数增加20倍，并在克隆水平上对高亲和力CD8(+)T细胞群体进行浓缩，所需的多肽剂量超过1log(10)--比未治疗的相应细胞少1倍。对经IL-21处理的T细胞进行表型分析，发现有一个独特的CD45RO(+)CD28(高)CD8(+)T细胞群体，该表型在IL-21作用后至少4wk内保持稳定。这些CD28(高)CD8(+)T细胞在抗原刺激下产生IL-2，是潜在的辅助性非依赖性CTL。我们的研究证明了IL-21在原发的抗原特异性的人类CTL反应中的重要作用，并支持将IL-21用于体外产生有效的抗原特异性CTL用于过继治疗或作为体内免疫期间的佐剂细胞因子来对抗肿瘤AGS。
IL-21, a newly described cytokine belonging to the IL-2 gamma-chain receptor cytokine family (that includes IL-2, IL-7, and IL-15), has been described as an important regulator of the cellular immune response. In this study, the role of IL-21 in the generation of a human Ag-specific CD8(+) T cell response is characterized by tracking a rare, but measurable population of self-Ag-specific T cells in vitro. Autologous dendritic cells pulsed with the melanoma antigen recognized T cells I self-peptide were used to stimulate CD8(+) T cells from HLA-A2(+) healthy donors and melanoma patients. We demonstrate that exposure to IL-21 increased the total number of MART-1-specific CD8(+) T cells that could be elicited by > 20-fold and, at the clonal level, enriched for a population of high-affinity CD8(+) T cells with a peptide dose requirement more than 1 log(10)-fold less than their untreated counterparts. Phenotypic analysis of T cells from IL-21-treated cultures revealed a unique population of CD45RO(+)CD28(high)CD8(+) T cells, a phenotype that was stable for at least 4 wk after IL-21 exposure. These CD28(high)CD8(+) T cells produced IL-2 upon Ag stimulation and represent potential helper-independent CTLs. Our studies demonstrate a significant role for IL-21 in the primary Ag-specific human CTL response and support the use of IL-21 in the ex vivo generation of potent Ag-specific CTLs for adoptive therapy or as an adjuvant cytokine during in vivo immunization against tumor Ags.