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注射未成熟树突状细胞后对人类效应T细胞功能的抗原特异性抑制。

Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells.

作者信息

Dhodapkar M V, Steinman R M, Krasovsky J, Munz C, Bhardwaj N

机构信息

Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021, USA.

出版信息

J Exp Med. 2001 Jan 15;193(2):233-8. doi: 10.1084/jem.193.2.233.

Abstract

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 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.

摘要

树突状细胞(DCs)的免疫刺激特性与其成熟状态相关。注射成熟的DCs可迅速增强人类抗原特异性CD4+和CD8+ T细胞免疫。在此,我们描述了两名健康受试者单次注射用流感基质肽(MP)和钥孔戚血蓝蛋白(KLH)脉冲处理的未成熟DCs后的免疫反应。与先前使用成熟DCs的研究结果相反,在两名受试者中注射未成熟DCs均导致新鲜分离的T细胞中MP特异性CD8+ T细胞效应功能的特异性抑制以及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细胞在培养中进行刺激时,免疫后MP特异性主要组织相容性复合体四聚体结合细胞数量更多,但这些细胞的干扰素产生减少且缺乏杀伤活性。这些数据证明了在人体内对效应T细胞功能进行抗原特异性抑制的可行性,并提醒在试图增强肿瘤或微生物免疫时使用未成熟DCs需谨慎。

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