Interactions between dendritic cells and regulatory T cells.

调节性T细胞（Tregs）是CD4+辅助性T细胞的一个亚群，表达转录因子Foxp3，可以通过多种机制抑制免疫反应，包括细胞因子的产生和DC功能的下调。在大多数情况下，treg不增殖，但我们之前已经证明骨髓树突状细胞（DCs）是刺激treg增殖和扩增的特化抗原呈递细胞。重要的是，通过dc扩增的treg维持Foxp3的表达，并且在体外和体内仍然具有抑制作用。具体来说，我们发现dc扩增的Tregs可以逆转NOD小鼠的糖尿病。然后我们假设，就像传统的T细胞被树突状细胞和抗原刺激一样，树突状细胞刺激的Tregs会上调对其抑制功能重要的转录本。因此，我们比较了受dc刺激的Tregs与静息Tregs或IL-2刺激的Tregs的转录谱。有趣的是，IL-1途径的天然抑制剂在树突状细胞刺激的treg中高度上调。我们现在正在研究IL-1抑制剂对Treg和Teff功能的作用。此外，将与Tregs培养的DCs的转录谱与单独培养的DCs进行比较。正如其他人报道的那样，我们也观察到在用Tregs培养的dc中参与抗原加工和递呈的转录本下调。我们现在关注的是一小部分转录本，这些转录本在treg培养后在dc中上调，而在无辅助T细胞（CD4+ CD25-细胞）培养后则没有上调。我们开始测试这些转录本在DC功能中的作用。

Regulatory T cells (Tregs) are a subset of CD4+ helper T cells that express the transcription factor Foxp3 and can suppress immune responses through a variety of mechanisms, including cytokine production and down-modulation of DC function. Under most conditions, Tregs do not proliferate, but we have previously shown that bone marrow dendritic cells (DCs) are specialized antigen presenting cells for stimulating proliferation and expansion of Tregs. Importantly, Tregs expanded by DCs maintain Foxp3 expression and are still suppressive in vitro and in vivo. Specifically, we showed that DC-expanded Tregs can reverse diabetes in NOD mice. We then hypothesized that, just as conventional T cells are optimally stimulated by DCs and antigen, Tregs stimulated with DCs would upregulate transcripts important for their suppressive function. Therefore, we have compared transcriptional profiles from Tregs stimulated with DCs, with profiles from resting Tregs or Tregs stimulated with IL-2. Interestingly, natural inhibitors of the IL-1 pathway were highly upregulated in Tregs stimulated by DCs. We are now studying the role of inhibitors of IL-1 for both Treg and Teff function. In addition, transcriptional profiles of DCs that had been cultured with Tregs were compared to DCs cultured alone. As reported by others, we also observed downregulation of transcripts involved in antigen processing and presentation in DCs that had been cultured with Tregs. We have now focused on a small set of transcripts that are upregulated in DCs after culture with Tregs, but not after culture with nave helper T cells (CD4+ CD25- cells). We are beginning to test the role of these transcripts for DC function.