Induction of interleukin 10-producing, nonproliferating CD4(+) T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells.
Induction of interleukin 10-producing, nonproliferating CD4(+) T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells.
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DOI：
10.1084/jem.192.9.1213
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发表时间：
2000-11-06
期刊：
影响因子：
--
通讯作者：
Enk AH
中科院分区：
文献类型：
--
作者：
Jonuleit H;Schmitt E;Schuler G;Knop J;Enk AH
树突状细胞（dc）的功能特性严格依赖于它们的成熟状态。为了分析树突状细胞成熟状态对T细胞启动和分化的影响，我们使用未成熟的CD83−和成熟的CD83+人树突状细胞刺激幼稚的同种异体CD4+ T细胞。成熟dc的重复刺激导致同种异体反应性T细胞的强烈扩增和辅助性T细胞1 （Th1）的专属发育。相反，在未成熟树突状细胞反复刺激后，同种反应性T细胞表现出不可逆的抑制增殖，这种抑制不能通过成熟树突状细胞或外周血单个核细胞再刺激或添加白细胞介素(IL)-2来恢复。只有成熟dc对T细胞的刺激导致CD154、CD69和CD70的上调，而未成熟dc激活的T细胞显示出负调节细胞毒性T淋巴细胞相关分子4 （CTLA-4）的早期上调。经过几次未成熟dc刺激后，这些T细胞失去了产生干扰素γ、IL-2或IL-4的能力，并分化为非增殖的、产生il -10的T细胞。此外，在共培养实验中，这些T细胞以接触和剂量依赖，但抗原非特异性的方式抑制抗原驱动的Th1细胞增殖。这些数据表明，未成熟和成熟的dc诱导不同类型的T细胞反应：成熟的dc诱导炎性Th1细胞，未成熟的dc诱导产生il -10的T细胞调节1样细胞。
The functional properties of dendritic cells (DCs) are strictly dependent on their maturational state. To analyze the influence of the maturational state of DCs on priming and differentiation of T cells, immature CD83− and mature CD83+ human DCs were used for stimulation of naive, allogeneic CD4+ T cells. Repetitive stimulation with mature DCs resulted in a strong expansion of alloreactive T cells and the exclusive development of T helper type 1 (Th1) cells. In contrast, after repetitive stimulation with immature DCs the alloreactive T cells showed an irreversibly inhibited proliferation that could not be restored by restimulation with mature DCs or peripheral blood mononuclear cells, or by the addition of interleukin (IL)-2. Only stimulation of T cells with mature DCs resulted in an upregulation of CD154, CD69, and CD70, whereas T cells activated with immature DCs showed an early upregulation of the negative regulator cytotoxic T lymphocyte–associated molecule 4 (CTLA-4). These T cells lost their ability to produce interferon γ, IL-2, or IL-4 after several stimulations with immature DCs and differentiated into nonproliferating, IL-10–producing T cells. Furthermore, in coculture experiments these T cells inhibited the antigen-driven proliferation of Th1 cells in a contact- and dose-dependent, but antigen-nonspecific manner. These data show that immature and mature DCs induce different types of T cell responses: inflammatory Th1 cells are induced by mature DCs, and IL-10–producing T cell regulatory 1–like cells by immature DCs.
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DOI：
10.1084/jem.184.2.741
发表时间：
1996-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.8
作者：
Pierre, P;Turley, SJ;Mellman, I
通讯作者：
Mellman, I
DOI：
10.1084/jem.180.4.1263
发表时间：
1994-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Caux C;Massacrier C;Vanbervliet B;Dubois B;Van Kooten C;Durand I;Banchereau J
通讯作者：
Banchereau J
影响因子：
5.4
作者：
Jonuleit, H;Kühn, U;Enk, AH
通讯作者：
Enk, AH
影响因子：
15.3
作者：
ROMANI, N;KOIDE, S;CROWLEY, M;WITMERPACK, M;LIVINGSTONE, AM;FATHMAN, CG;INABA, K;STEINMAN, RM
通讯作者：
STEINMAN, RM