Oldenhove Guillaume, de Heusch Magali, Urbain-Vansanten Georgette, Urbain Jacques, Maliszewski Charlie, Leo Oberdan, Moser Muriel
Laboratoire de Physiologie Animale, Université Libre de Bruxelles, Rue des Prof. Jeener et Brachet, 12, 6041 Gosselies, Belgium.
J Exp Med. 2003 Jul 21;198(2):259-66. doi: 10.1084/jem.20030654.
Recent evidence suggests that in addition to their well known stimulatory properties, dendritic cells (DCs) may play a major role in peripheral tolerance. It is still unclear whether a distinct subtype or activation status of DC exists that promotes the differentiation of suppressor rather than effector T cells from naive precursors. In this work, we tested whether the naturally occurring CD4+ CD25+ regulatory T cells (Treg) may control immune responses induced by DCs in vivo. We characterized the immune response induced by adoptive transfer of antigen-pulsed mature DCs into mice depleted or not of CD25+ cells. We found that the development of major histocompatibility complex class I and II-restricted interferon gamma-producing cells was consistently enhanced in the absence of Treg. By contrast, T helper cell (Th)2 priming was down-regulated in the same conditions. This regulation was independent of interleukin 10 production by DCs. Of note, splenic DCs incubated in vitro with Toll-like receptor ligands (lipopolysaccharide or CpG) activated immune responses that remained sensitive to Treg function. Our data further show that mature DCs induced higher cytotoxic activity in CD25-depleted recipients as compared with untreated hosts. We conclude that Treg naturally exert a negative feedback mechanism on Th1-type responses induced by mature DCs in vivo.
最近的证据表明，除了其众所周知的刺激特性外，树突状细胞（DCs）可能在外周免疫耐受中起主要作用。目前尚不清楚是否存在促进抑制性T细胞而非效应性T细胞从幼稚前体分化的独特DC亚型或激活状态。在这项研究中，我们测试了天然存在的CD4+CD25+调节性T细胞（Treg）是否可以在体内控制DCs诱导的免疫反应。我们对将抗原脉冲成熟DCs过继转移到CD25+细胞耗尽或未耗尽的小鼠中所诱导的免疫反应进行了表征。我们发现，在没有Treg的情况下，主要组织相容性复合体I类和II类限制性产生干扰素γ的细胞的发育持续增强。相比之下，在相同条件下，辅助性T细胞（Th）2启动被下调。这种调节独立于DCs产生的白细胞介素10。值得注意的是，体外与Toll样受体配体（脂多糖或CpG）孵育的脾DCs激活的免疫反应对Treg功能仍然敏感。我们的数据进一步表明，与未处理的宿主相比，成熟DCs在CD25耗尽的受体中诱导了更高的细胞毒性活性。我们得出结论，Treg在体内对成熟DCs诱导的Th1型反应自然发挥负反馈机制。
