Toll-like receptor 2 controls expansion and function of regulatory T cells
Toll-like receptor 2 controls expansion and function of regulatory T cells
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DOI：
10.1172/jci25439
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发表时间：
2006-02-01
影响因子：
15.9
通讯作者：
Adema, GJ
中科院分区：
文献类型：
--
作者：
Sutmuller, RPM;den Brok, MHMGM;Adema, GJ
在抑制免疫反应和预防对宿主有害的自身免疫反应中，TGFAP起着核心作用。然而，在急性感染过程中，TcR可能会阻碍效应T细胞的活性，直接消除病原体的挑战。由先天免疫细胞表达的来自TLR家族的病原体识别受体对于有效免疫的产生至关重要。我们最近发现，与WT同窝对照小鼠相比，TLR 2（-/-）小鼠中的CD 4（+）CD 25（+）Treg亚群的数量显著减少，这表明了Treg与TLR 2之间的联系。在这里，我们报道了TLR 2配体Pam（3）Cys，而不是LPS（TLR 4）或CpG（TLR 9），以MyD 88依赖的方式直接作用于纯化的TcR。此外，当与TCR刺激组合时，TLR 2触发增强了体外和体内Treg增殖，并通过直接影响TCR而导致体外抑制性Treg表型的暂时丧失。重要的是，过继转移到TLR 2（-/-）小鼠中的WT Tclase在白色念珠菌感染的急性期通过全身施用TLR 2配体而被中和，导致100倍减少的C.白色念珠菌生长。这表明，体内TLR 2也控制Tcl 3的功能，并建立了TLR和通过Tcl 3控制免疫应答之间的直接联系。
Tregs play a central role in the suppression of immune reactions and prevention of autoimmune responses harmful to the host. During acute infection, however, Tregs might hinder effector T cell activity directed toward the elimination of the pathogenic challenge. Pathogen recognition receptors from the TLR family expressed by innate immune cells are crucial for the generation of effective immunity. We have recently shown the CD4(+)CD25(+) Treg subset in TLR2(-/-) mice to be significantly reduced in number compared with WT litter-mate control mice, indicating a link between Tregs and TLR2. Here, we report that the TLR2 ligand Pam(3)Cys, but not LPS (TLR4) or CpG (TLR9), directly acts on purified Tregs in a MyD88-dependent fashion. Moreover, when combined with TCR stimulation, TLR2 triggering augmented Treg proliferation in vitro and in vivo and resulted in a temporal loss of the suppressive Treg phenotype in vitro by directly affecting Tregs. Importantly, WT Tregs adoptively transferred into TLR2(-/-) mice were neutralized by systemic administration of TLR2 ligand during the acute phase of a Candida albicans infection, resulting in a 100-fold reduced C. albicans outgrowth. This demonstrates that in vivo TLR2 also controls the function of Tregs and establishes a direct link between TLRs and the control of immune responses through Tregs.