Department of Microbiology & Immunology, Columbia University, College of Physicians & Surgeons, New York, NY 10032, USA.
Immunity. 2010 Nov 24;33(5):791-803. doi: 10.1016/j.immuni.2010.10.014. Epub 2010 Nov 11.
Immune tolerance against enteric commensal bacteria is important for preventing intestinal inflammation. Deletion of phosphoinositide-dependent protein kinase 1 (Pdk1) in T cells via Cd4-Cre induced chronic inflammation of the intestine despite the importance of PDK1 in T cell activation. Analysis of colonic intraepithelial lymphocytes of PDK1-deficient mice revealed markedly increased CD8α(+) T cell receptor (TCR)γδ(+) T cells, including an interleukin-17 (IL-17)-expressing population. TCRγδ(+) T cells were responsible for the inflammatory colitis as shown by the fact that deletion of Tcrd abolished spontaneous colitis in the PDK1-deficient mice. This dysregulation of intestinal TCRγδ(+) T cells was attributable to a reduction in the number and functional capacity of PDK1-deficient T regulatory (Treg) cells. Adoptive transfer of wild-type Treg cells abrogated the spontaneous activation and proliferation of intestinal TCRγδ(+) T cells observed in PDK1-deficient mice and prevented the development of colitis. Therefore, suppression of intestinal TCRγδ(+) T cells by Treg cells maintains enteric immune tolerance.
针对肠道共生菌的免疫耐受对于预防肠道炎症很重要。通过 Cd4-Cre 对 T 细胞中磷酸肌醇依赖性蛋白激酶 1（PDK1）的缺失导致肠道慢性炎症，尽管 PDK1 在 T 细胞激活中很重要。对 PDK1 缺陷小鼠结肠上皮内淋巴细胞的分析显示，CD8α(+)T 细胞受体（TCR）γδ(+)T 细胞明显增加，包括表达白细胞介素-17（IL-17）的群体。TCRγδ(+)T 细胞是炎症性结肠炎的罪魁祸首，因为 Tcrd 的缺失消除了 PDK1 缺陷小鼠自发发生的结肠炎。肠道 TCRγδ(+)T 细胞的这种失调归因于 PDK1 缺陷性调节性（Treg）细胞数量和功能能力的降低。野生型 Treg 细胞的过继转移消除了在 PDK1 缺陷小鼠中观察到的肠道 TCRγδ(+)T 细胞的自发激活和增殖，并防止了结肠炎的发展。因此，Treg 细胞对肠道 TCRγδ(+)T 细胞的抑制维持了肠道免疫耐受。
