Bishop Kenneth D, Harris John E, Mordes John P, Greiner Dale L, Rossini Aldo A, Czech Michael P, Phillips Nancy E
University of Massachusetts Medical School, Worcester, 01655, USA.
Cell Immunol. 2009;256(1-2):86-91. doi: 10.1016/j.cellimm.2009.01.008. Epub 2009 Feb 23.
Recent studies have implicated the cell surface receptor Programmed Death-1 (PD-1) in numerous models of T cell anergy, though the specific mechanisms by which the PD-1 signal maintains tolerance is not clear. We demonstrate that the depletion of PD-1 with siRNA results in a complete reversal of clonal anergy in the A.E7 T cell model, suggesting that the mechanism by which PD-1 maintains the anergic phenotype is a T-cell-intrinsic phenomenon, and not one dependent on other cell populations in vivo. We have also shown that the neutralization of IL-2 during restimulation abrogates the effect of PD-1 depletion, suggesting that tolerance mediated by PD-1 is wholly IL-2 dependent, and likewise intrinsic to the tolerized cells.
近期研究表明，细胞表面受体程序性死亡蛋白1（PD-1）在众多T细胞无能模型中发挥作用，不过PD-1信号维持免疫耐受的具体机制尚不清楚。我们证明，在A.E7 T细胞模型中，用小干扰RNA（siRNA）去除PD-1可使克隆无能完全逆转，这表明PD-1维持无能表型的机制是一种T细胞内在现象，而非依赖体内其他细胞群体。我们还表明，在再次刺激期间中和白细胞介素-2（IL-2）可消除去除PD-1的效果，这表明由PD-1介导的免疫耐受完全依赖IL-2，同样也是耐受细胞所固有的。
