Gr-1intCD11b+ myeloid-derived suppressor cells accumulate in corneal allograft and improve corneal allograft survival
Gr-1intCD11b+ myeloid-derived suppressor cells accumulate in corneal allograft and improve corneal allograft survival
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DOI：
10.1189/jlb.5a1115-508rr
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发表时间：
2016-12-01
影响因子：
5.5
通讯作者：
Lee, Hyung Keun
中科院分区：
文献类型：
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作者：
Choi, Wungrak;Ji, Yong Woo;Lee, Hyung Keun
我们鉴定了髓系来源的抑制细胞(MDSCs)的特性，并利用小鼠同种异体角膜移植模型研究了它们的诱导机制及其在同种异体角膜移植排斥反应中的作用。在小鼠中，MDSCs共表达CD11b和Gr-1CD11b(+)细胞，Gr-1(+)CD11b(+)细胞在术后4d~4wk渗入同种异体角膜，但Gr-1(+)CD11b(+)细胞在接受和排斥同种异体移植的小鼠之间、外周血和骨髓中的频率没有差异。值得注意的是，Gr-1(Int)CD11b(+)细胞，而不是Gr-1(Hi)CD11b(+)细胞，在术后早期渗透到接受的移植物中，并表达高水平的免疫抑制细胞因子，包括IL-10、转化生长因子-β和肿瘤坏死因子相关的凋亡诱导配体。这一群体一直持续到手术后4周。Gr-1(Int)CD11b(+)细胞在体外只有高剂量(100 ng/ml)的干扰素-γ(>；100 ng/ml)联合GM-CSF才能诱导免疫抑制细胞因子的表达。此外，过继转移Gr-1(Int)CD11b(+)细胞减少了T细胞的渗透，从而提高了移植物的存活率。综上所述，同种异体角膜移植物Gr-1(Int)CD11b(+)MDSCs的发育过程中，大剂量的干扰素-γ是必不可少的，而在同种异体角膜移植早期微小的环境变化可能会导致移植物存活率的巨大差异。
We identified the characteristics of myeloid-derived suppressor cells (MDSCs) and investigated their mechanism of induction and their functional role in allograft rejection using a murine corneal allograft model. In mice, MDSCs coexpress CD11b and myeloid differentiation antigen Gr-1.Gr-1(+)CD11b(+) cells infiltrated allografted corneas between 4 d and 4 wk after surgery; however, the frequencies of Gr-1(+)CD11b(+) cells were not different between accepted and rejected allografts or in peripheral blood or BM. Of interest, Gr-1(int)CD11b(+) cells, but not Gr-1(hi)CD11b(+) cells, infiltrated the accepted graft early after surgery and expressed high levels of immunosuppressive cytokines, including IL-10, TGF-beta, and TNF-related apoptosis-inducing ligand. This population remained until 4 wk after surgery. In vitro, only high dose (>100 ng/ml) of IFN-gamma plus GM-CSF could induce immunosuppressive cytokine expression in Gr-1(int)CD11b(+) cells. Furthermore, adoptive transfer of Gr-1(int)CD11b(+) cells reduced T cell infiltration, which improved graft survival. In conclusion, high-dose IFN-gamma in allograft areas is essential for development of Gr-1(int)CD11b(+) MDSCs in corneal allografts, and subtle environmental changes in the early period of the allograft can result in a large difference in graft survival.