Zhao Xiang-Yu, Wang Yu-Tong, Mo Xiao-Dong, Zhao Xiao-Su, Wang Ya-Zhe, Chang Ying-Jun, Huang Xiao-Jun
Peking University People's Hospital and Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11 Xizhimen South Street, Beijing, 100044, China.
Peking-Tsinghua Center for Life Sciences, Beijing, 100871, China.
J Transl Med. 2015 May 7;13:145. doi: 10.1186/s12967-015-0507-z.
Regulatory T cells (Treg) in allografts are important for the prevention of graft-versus-host disease (GVHD) post-transplantation. The aim of this study was to compare the contents of Tregs and effector T cells in granulocyte colony-stimulating factor (G-CSF)-primed bone marrow grafts (G-BM) and peripheral blood grafts (G-PB).
G-BM and G-PB were obtained from 20 allogeneic donors. T-cell subgroups, including conventional T cells and different types of Treg cells, as well as the percentage of Ki67 expression on CD4(+)CD25(high)Foxp3(+) Treg cells, were analyzed using flow cytometry. The levels of interferon-γ (IFN-γ) and interleukin-17 (IL-17) secreted by T cells stimulated with PMA and ionomycin were also determined by flow cytometry.
The percentage of CD4(+)CD25(high)CD127(-/dim)CD62L(+) Treg cells was significantly higher in the G-BM group, with higher proportions of CD45RA(+) naïve Treg cells and higher expression of CD69 on Treg cells in G-BM (P < 0.05). The percentage of Ki67 expression in CD4(+)CD25(high)Foxp3(+) Treg cells in G-BM was significantly higher than that on G-PB. The suppressive functions of Treg cells in inhibiting T-cell activation were comparable between G-BM and G-PB. The proportions of CD4(+)CD25(-)CD69(+) Treg subsets as well as Th1 cells in G-BM were also significantly higher than those in G-PB (P < 0.001). The proportions of conventional T cells and Th17 effector cells were comparable in G-BM compared with those in G-PB. Thus, the ratio of conventional T cells and CD4(+)CD25(high)CD127(-/dim) regulatory T cells were lower in G-BM than that in G-PB (P = 0.014).
In addition to the much higher T-cell counts in G-PB grafts that may contribute to more severe GVHD, the higher frequency of Treg cells and lower ratio of conventional T cells to Treg cells in G-BM compared with G-PB grafts might reduce GVHD post-transplantation in G-BM compared with G-PB transplantation.
移植器官中的调节性T细胞（Treg）对于预防移植后移植物抗宿主病（GVHD）至关重要。本研究旨在比较粒细胞集落刺激因子（G-CSF）预处理的骨髓移植物（G-BM）和外周血移植物（G-PB）中Treg细胞和效应T细胞的含量。
从20名同种异体供体获取G-BM和G-PB。使用流式细胞术分析T细胞亚群，包括传统T细胞和不同类型的Treg细胞，以及CD4(+)CD25(high)Foxp3(+) Treg细胞上Ki67的表达百分比。还用流式细胞术测定了用佛波酯（PMA）和离子霉素刺激的T细胞分泌的干扰素-γ（IFN-γ）和白细胞介素-17（IL-17）水平。
G-BM组中CD4(+)CD25(high)CD127(-/dim)CD62L(+) Treg细胞的百分比显著更高，G-BM中CD45RA(+) 幼稚Treg细胞比例更高，且Treg细胞上CD69的表达更高（P < 0.05）。G-BM中CD4(+)CD25(high)Foxp3(+) Treg细胞中Ki67的表达百分比显著高于G-PB。G-BM和G-PB中Treg细胞抑制T细胞活化的抑制功能相当。G-BM中CD4(+)CD25(-)CD69(+) Treg亚群以及Th1细胞的比例也显著高于G-PB（P < 0.001）。与G-PB相比，G-BM中传统T细胞和Th17效应细胞的比例相当。因此，G-BM中传统T细胞与CD4(+)CD25(high)CDr127(-/dim)调节性T细胞的比例低于G-PB（P = 0.014）。
除了G-PB移植物中T细胞数量多得多可能导致更严重的GVHD外，与G-PB移植物相比，G-BM中Treg细胞频率更高且传统T细胞与Treg细胞的比例更低，这可能使G-BM移植后GVHD比G-PB移植时减少。
