Interactions between dendritic cells and regulatory T cells.

调节性T细胞(Tregs)是CD4+辅助T细胞的一个亚群，表达转录因子Foxp3，可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，树突状细胞不会增殖，但我们之前已经证明，骨髓树突状细胞(DC)是刺激树突状细胞增殖和扩增的特异性抗原提呈细胞。重要的是，树突状细胞扩增的树突状细胞维持Foxp3的表达，在体外和体内仍具有抑制作用。具体地说，我们证明了DC扩展的Tregs可以逆转NOD小鼠的糖尿病。然后我们假设，就像传统的T细胞受到DC和抗原的最佳刺激一样，DC刺激的Tregs将上调对其抑制功能至关重要的转录。因此，我们比较了树突状细胞刺激的树突状细胞的转录图谱与静息树突状细胞或IL-2刺激的树突状细胞的转录图谱。有趣的是，IL-1途径的天然抑制物在DC刺激的Treg中高度上调。我们现在正在研究IL-1的抑制剂对Treg功能和新Treg的诱导的作用。此外，还比较了与Tregs共同培养的DC和单独培养的DC的转录谱。正如其他人所报道的，我们还观察到与Treg一起培养的DC中涉及抗原处理和提呈的转录下调。我们现在关注的是一小部分转录本，这些转录本在Tregs培养后在DC中上调，但在与NAVE辅助T细胞(CD4+CD25-细胞)培养后不上调。我们开始测试这些转录本对DC功能的作用。

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 function and induction of new Tregs. 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.