Prolonged antigen storage endows merocytic dendritic cells with enhanced capacity to prime anti-tumor responses in tumor-bearing mice.
Prolonged antigen storage endows merocytic dendritic cells with enhanced capacity to prime anti-tumor responses in tumor-bearing mice.
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DOI：
10.4049/jimmunol.1001619
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发表时间：
2010-09-15
期刊：
影响因子：
--
通讯作者：
Janssen EM
中科院分区：
文献类型：
--
作者：
Reboulet RA;Hennies CM;Garcia Z;Nierkens S;Janssen EM
用照射的自体肿瘤细胞接种肿瘤细胞是一种很有前途的方法，可以在不需要肿瘤抗原鉴定的情况下激活肿瘤特异性T细胞反应。然而，DC摄取死亡细胞通常是一种非炎症性或耐受性事件，以防止自身反应性免疫反应的发展。在这里，我们描述了最近发现的一群DC(MercyticDC，MCDC)具有强大的T细胞启动能力的机制，该DC在摄取凋亡细胞时，能够有效地启动CD8+和CD4+T细胞对细胞相关抗原的启动。McDC通过分生组织吞噬过程获得细胞相关物质，该过程定义为摄取长期储存在非酸性隔间中的小颗粒，持续的抗原提呈，以及I型干扰素的诱导。MCDC对细胞相关抗原诱导的T细胞表现为原代扩增增加，效应器功能增强，记忆形成增加。利用转基因T细胞转移模型和内源性模型，我们发现，暴露在濒临死亡的肿瘤细胞中的MCDC治疗荷瘤小鼠，通过激活幼稚的肿瘤特异性CD8+T细胞以及恢复体内肿瘤无反应的肿瘤特异性T细胞，导致肿瘤抑制和宿主存活增加。在免疫抑制条件下，巨噬细胞树突状细胞能够刺激CD4+和CD8+T细胞与细胞相关抗原结合，使其成为肿瘤治疗以及自身免疫和移植的干预策略的靶点。
Tumor-cell vaccination with irradiated autologous tumor cells is a promising approach to activate tumor-specific T cell responses without the need for tumor antigen identification. However, uptake of dying cells by DC is generally a non-inflammatory or tolerizing event in order to prevent the development of autoreactive immune responses. Here we describe the mechanisms that confer the potent T cell priming capacity of a recently identified a population of DC (merocyticDC, mcDC) that potently primes both CD8+ and CD4+ T cells to cell-associated antigens upon uptake of apoptotic cells. mcDCs acquired cell-associated materials though a process of merocytosis that is defined by the uptake of small particles that are stored in non-acidic compartments for prolonged periods, sustained antigen presentation, and the induction of type I IFN. T cells primed by mcDC to cell-associated antigens exhibit increased primary expansion, enhanced effector function and increased memory formation. Using transgenic T cell transfer models and endogenous models, we show that treatment of tumor-bearing mice with mcDC that have been exposed to dying tumor cells results in tumor suppression and increased host survival through the activation of naïve tumor-specific CD8+ T cells as well as the revigoration of tumor-specific T cells that had been rendered non-responsive by the tumor in vivo. The potent capacity of mcDCs to prime both CD4+ and CD8+ T cells to cell-associated antigens under immunosuppressive conditions makes this DC subset an attractive target for tumor therapies as well as interventional strategies for autoimmunity and transplantation.
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影响因子：
4.4
作者：
Bedoui, Sammy;Prato, Sandro;Segura, Elodie
通讯作者：
Segura, Elodie
影响因子：
4.4
作者：
Hamilton-Williams, EE;Lang, A;Kurts, C
通讯作者：
Kurts, C
影响因子：
4.4
作者：
Bellone, M;Cantarella, D;Dellabona, P
通讯作者：
Dellabona, P
DOI：
10.1084/jem.185.6.1101
发表时间：
1997-03-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Grouard G;Rissoan MC;Filgueira L;Durand I;Banchereau J;Liu YJ
通讯作者：
Liu YJ
影响因子：
30.5
作者：
Kaech, SM;Ahmed, R
通讯作者：
Ahmed, R