Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
Sci Rep. 2016 Dec 23;6:39924. doi: 10.1038/srep39924.
Regulatory T cells (Tregs) are crucial for allograft survival. Tregs can be divided into thymus-derived natural Tregs (tTregs) and peripherally-derived induced Tregs (pTregs). Here, we determine whether the suppressive function of Treg subsets is hampered in hosts who are at high risk for rejecting their graft. To induce graft beds that promote high risk of transplant rejection, intrastromal corneal sutures were placed two weeks prior to the transplant procedure in mice. We demonstrate that in high-risk recipients the frequencies and function of pTregs (but not tTregs) are suppressed. Reduced function of pTregs correlated with decreased expression of CTLA-4, interleukin-10, and transforming growth factor-β. Adoptive transfer of pTregs from mice at low risk of subsequent graft rejection is able to rescue graft survival in recipients that are at high risk of rejecting their grafts. Our data suggest that impaired function of pTregs, but not tTregs, mediates the loss of immune tolerance and promotes allograft rejection.
调节性 T 细胞（Tregs）对于同种异体移植物的存活至关重要。Tregs 可以分为胸腺来源的天然 Tregs（tTregs）和外周诱导的 Tregs（pTregs）。在这里，我们确定在对移植物有高排斥风险的宿主中，Treg 亚群的抑制功能是否受到阻碍。为了诱导促进移植排斥高风险的移植物床，我们在移植前两周在小鼠的角膜基质中放置了间质缝线。我们证明，在高风险受者中，pTregs（而不是 tTregs）的频率和功能受到抑制。pTregs 功能降低与 CTLA-4、白细胞介素-10 和转化生长因子-β 的表达降低相关。从排斥风险较低的小鼠中过继转移 pTregs，能够挽救排斥风险高的受者的移植物存活。我们的数据表明，pTregs 功能障碍而不是 tTregs 功能障碍介导了免疫耐受的丧失，并促进了同种异体移植物排斥。
