DNA vaccination with all-trans retinoic acid treatment induces long-term survival and elicits specific immune responses requiring CD4+ and CD8+ T-cell activation in an acute promyelocytic leukemia mouse model
DNA vaccination with all-trans retinoic acid treatment induces long-term survival and elicits specific immune responses requiring CD4+ and CD8+ T-cell activation in an acute promyelocytic leukemia mouse model
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DOI：
10.1182/blood-2007-08-109009
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发表时间：
2010-01-21
期刊：
影响因子：
20.3
通讯作者：
Padua, Rose Ann
中科院分区：
文献类型：
--
作者：
Furugaki, Kouichi;Pokorna, Katerina;Padua, Rose Ann
DNA疫苗接种和全反式维甲酸（ATRA）导致急性早幼粒细胞白血病（APL）小鼠模型的生存优势。CD 4（+）或CD 8（+）细胞的耗竭可消除这种效应。长期存活者的CD 4（+）耗竭导致3个月内复发和死亡，从而证明了CD 4（+）和CD 8（+）亚群对于产生DNA驱动的抗白血病免疫应答的需要，并强调了CD 4（+）细胞在维持持久缓解中的关键作用。脱粒和细胞毒性羧基荧光素二乙酸琥珀酰亚胺酯为基础的测定显示主要组织相容性复合物限制APL特异性T细胞介导的免疫反应。分选的APL特异性CD 8（+）CD 107 a（+）T细胞显示抗白血病活性增加。当用APL细胞或来自早幼粒细胞白血病-RAR α疫苗衍生序列的肽刺激时，显示来自ATRA + DNA处理的小鼠的效应物分泌干扰素-γ，如通过ELISpot测定检测的。我们的研究结果表明，DNA疫苗与全反式维甲酸赋予有效的提高干扰素-γ-生产和细胞毒性T细胞在白血病小鼠。（血。2010; 115：653-656）
DNA vaccination and all-trans retinoic acid (ATRA) result in a survival advantage in a mouse model of acute promyelocytic leukemia (APL). Depletion of CD4(+) or CD8(+) cells abolished this effect. CD4(+) depletions of long-term survivors resulted in relapse and death within 3 months, thus demonstrating the need of both CD4(+) and CD8(+) subsets for the generation of DNA-driven antileukemic immune responses and underscoring a crucial role of CD4(+) cells in the maintenance of durable remissions. Degranulation and cytotoxic carboxyfluorescein diacetate succinimidyl ester-based assays showed major histocompatibility complex restricted APL-specific T cell-mediated immune responses. Sorted APL-specific CD8(+)CD107a(+) T cells showed an increase of antileukemic activity. Effectors from ATRA + DNA-treated mice were shown to secrete interferon-gamma when stimulated with either APL cells or peptides from the promyelocytic leukemia-RAR alpha vaccine-derived sequences as detected by ELISpot assays. Our results demonstrate that DNA vaccination with ATRA confers the effective boosting of interferon-gamma-producing and cytotoxic T cells in the leukemic mice. (Blood. 2010; 115: 653-656)