Jang I K, Yoon H H, Yang M S, Lee J E, Lee D-H, Lee M W, Kim D S, Park J E
Department of Pediatrics, Ajou University School of Medicine, Suwon, Republic of Korea; Biomedical Research Institute, Lifeliver Co Ltd, Yongin, Republic of Korea.
Dongguk University Research Institute of Biotechnology, Dongguk University, Seoul, Republic of Korea.
Transplant Proc. 2014 Jun;46(5):1638-41. doi: 10.1016/j.transproceed.2013.12.059.
B7-H1 on mesenchymal stem cells (MSCs) is known to modulate immune response. However, its expression pattern and exact immunomodulatory mechanism are unclear. In this study, we examined the immunomodulatory mechanism through the expression pattern of B7-H1 and major histocompatibility complex class II in various MSCs. Human bone marrow, adipose tissue, and cord blood MSCs were isolated and cultured. B7-H1, HLA-ABC, and HLA-DR expression on MSCs by interferon-γ (IFN-γ) was detected time-dependently by flow cytometry. The inhibitory effect of MSCs on T lymphocytes was observed in phytohemagglutinin antigen-induced T cell proliferation assay. The expression of B7-H1 was rapidly induced, but the expression of HLA-DR was induced at 48 hours after IFN-γ treatment. The inhibitory effect of MSCs on T cell proliferation could be restored when the anti-B7-H1 monoclonal antibody was used to block the B7-H1, or when the HLA-DRα small interfering RNA was used to interfere with its expression. These results show that MSCs could inhibit the T cell proliferation and activation by B7-H1 depending on the presence of HLA-DR. Therefore, MSCs would have a strong effect on immune diseases such as graft-versus-host disease and autoimmune diseases when MSCs are primed with IFN-γ 48 hours before transplantation.
已知间充质干细胞（MSC）上的B7-H1可调节免疫反应。然而，其表达模式和确切的免疫调节机制尚不清楚。在本研究中，我们通过检测不同MSC中B7-H1和主要组织相容性复合体II类分子的表达模式来研究免疫调节机制。分离并培养人骨髓、脂肪组织和脐血来源的MSC。通过流式细胞术检测干扰素-γ（IFN-γ）作用下MSC上B7-H1、HLA-ABC和HLA-DR的表达随时间的变化。在植物血凝素抗原诱导的T细胞增殖试验中观察MSC对T淋巴细胞的抑制作用。IFN-γ处理后，B7-H1的表达迅速被诱导，但HLA-DR的表达在48小时后才被诱导。当使用抗B7-H1单克隆抗体阻断B7-H1，或使用HLA-DRα小干扰RNA干扰其表达时，MSC对T细胞增殖的抑制作用可恢复。这些结果表明，MSC可通过依赖HLA-DR的B7-H1抑制T细胞增殖和活化。因此，在移植前48小时用IFN-γ预处理MSC，其对移植物抗宿主病和自身免疫性疾病等免疫疾病将具有强大作用。
