Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH, USA.
Eur J Immunol. 2010 Jul;40(7):2006-15. doi: 10.1002/eji.200939387.
Recent studies have suggested Fas-mediated elimination of antigen-presenting cells as an important mechanism down-regulating the induction of autoimmune responses. It remains unknown whether this mechanism restricts the magnitude of immune responses to non-self antigens. We used a mouse model of a cutaneous CD8(+) T-cell-mediated immune response (contact hypersensitivity, CHS) to test if CD4(+)CD25(+) T cells expressing FasL regulate hapten-specific effector CD8(+) T cell expansion through the elimination of Fas-expressing hapten-presenting DC. In WT mice, attenuation of CD4(+)CD25(+) T regulatory cell activity by anti-CD25 mAb increased hapten-presenting DC numbers in skin-draining LN, which led to increased effector CD8(+) T-cell priming for CHS responses. In contrast, CD4(+)CD25(+) T cells did not regulate hapten-specific CD8(+) T-cell priming and CHS responses initiated by Fas-defective (lpr) DC. Thus, restricting DC priming functions through Fas-FasL interactions is a potent mechanism employed by CD4(+)CD25(+) regulatory cells to restrict CD8(+) T-cell-mediated allergic immune responses in the skin.
最近的研究表明，Fas 介导的抗原呈递细胞的消除是下调自身免疫反应诱导的一个重要机制。目前尚不清楚该机制是否限制了对非自身抗原的免疫反应的幅度。我们使用一种皮肤 CD8(+) T 细胞介导的免疫反应（接触过敏，CHS）的小鼠模型来测试 FasL 表达的 CD4(+)CD25(+) T 细胞是否通过消除 Fas 表达的呈递半抗原的 DC 来调节半抗原特异性效应 CD8(+) T 细胞的扩增。在 WT 小鼠中，通过抗 CD25 mAb 衰减 CD4(+)CD25(+) T 调节性细胞的活性增加了皮肤引流 LN 中的半抗原呈递 DC 的数量，这导致 CHS 反应的效应 CD8(+) T 细胞的初始增加。相比之下，Fas 缺陷（lpr）DC 引发的 CD4(+)CD25(+) T 细胞并不调节半抗原特异性 CD8(+) T 细胞的初始和 CHS 反应。因此，通过 Fas-FasL 相互作用限制 DC 初始功能是 CD4(+)CD25(+)调节性细胞在皮肤中限制 CD8(+) T 细胞介导的过敏免疫反应的一种有效机制。
