Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells.
Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells.
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DOI：
10.1084/jem.193.2.233
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发表时间：
2001-01-15
影响因子：
15.3
通讯作者：
Bhardwaj, N
中科院分区：
文献类型：
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作者：
Dhodapkar, M V;Steinman, R M;Krasovsky, J;Munz, C;Bhardwaj, N
树突状细胞（DC）的免疫刺激特性与其成熟状态有关。注射成熟DC可快速增强人的抗原特异性CD4+和CD8+ T细胞免疫。在这里，我们描述了两个健康受试者单次注射未成熟的树突状细胞与流感病毒基质肽（MP）和钥孔血蓝蛋白（KLH）脉冲的免疫反应。与先前使用成熟DC的研究结果相反，在两个受试者中注射未成熟DC导致新鲜分离的T细胞中MP特异性CD8+ T细胞效应子功能的特异性抑制和MP特异性白细胞介素10产生细胞的出现。当免疫前和免疫后的T细胞在培养中加强时，免疫后有更多数量的MP特异性主要组织相容性复合物四聚体结合细胞，但这些细胞减少了干扰素γ的产生，缺乏杀伤活性。这些数据证明了抗原特异性抑制效应T细胞功能在人体内的可行性，并敦促谨慎使用未成熟的DC时，试图增强肿瘤或微生物免疫。
Immunostimulatory properties of dendritic cells (DCs) are linked to their maturation state. Injection of mature DCs rapidly enhances antigen-specific CD4+ and CD8+ T cell immunity in humans. Here we describe the immune response to a single injection of immature DCs pulsed with influenza matrix peptide (MP) and keyhole limpet hemocyanin (KLH) in two healthy subjects. In contrast to prior findings using mature DCs, injection of immature DCs in both subjects led to the specific inhibition of MP-specific CD8+ T cell effector function in freshly isolated T cells and the appearance of MP-specific interleukin 10–producing cells. When pre- and postimmunization T cells were boosted in culture, there were greater numbers of MP-specific major histocompatibility complex tetramer-binding cells after immunization, but these had reduced interferon γ production and lacked killer activity. These data demonstrate the feasibility of antigen-specific inhibition of effector T cell function in vivo in humans and urge caution with the use of immature DCs when trying to enhance tumor or microbial immunity.