Impaired Function of Peripherally Induced Regulatory T Cells in Hosts at High Risk of Graft Rejection
Impaired Function of Peripherally Induced Regulatory T Cells in Hosts at High Risk of Graft Rejection
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DOI：
10.1038/srep39924
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发表时间：
2016-12-23
影响因子：
4.6
通讯作者：
Dana, Reza
中科院分区：
文献类型：
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作者：
Inomata, Takenori;Hua, Jing;Dana, Reza
调节性T细胞（TCRs）对同种异体移植物存活至关重要。胸腺肽可分为胸腺源性天然胸腺肽（tTHBE）和外周源性诱导胸腺肽（pTHBE）。在这里，我们确定Treg亚群的抑制功能是否在排斥移植物的高风险宿主中受到阻碍。为了诱导促进移植排斥高风险的移植床，在小鼠移植手术前两周放置角膜基质内缝线。我们证明，在高风险的收件人的频率和功能的pTdR（但不是tTdR）被抑制。pT细胞功能的降低与CTLA-4、白细胞介素-10和转化生长因子-β的表达降低相关。从随后移植物排斥风险低的小鼠中连续转移pT细胞能够挽救处于排斥移植物高风险的受体中的移植物存活。我们的数据表明，受损的功能pTcR，但不是tTcR，介导的免疫耐受的损失，促进同种异体移植排斥反应。
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-beta. 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.