Zhi-Gang Zhao, Wei-Ming Li, Zhi-Chao Chen, Yong You, Ping Zou
Department of Hematology and Oncology, the Oncology Hospital of Tianjin Medical University, Tianjin, PR China.
Leuk Lymphoma. 2008 Nov;49(11):2187-95. doi: 10.1080/10428190802455875.
Mesenchymal stem cells (MSCs) have received much attention because of their capabilities of differentiating into multiple mesenchymal lineages and supporting hematopoiesis. Recently, MSCs have gained further interests after the demonstration of an immunosuppressive role. However, it's still unclear whether the immunosuppressive capability of MSCs will be altered with disease state. In this study, our results showed that MSCs derived from patients with lymphoblastic leukemia (ALL), Hodgkin disease (HD), and non-Hodgkin lymphoma (NHL) capable of suppressing the proliferation of T-lymphocyte stimulated in a mixed-lymphocyte reaction (MLR). The immunosuppressive effect of MSCs derived from ALL, HD and NHL on T-cell proliferation was dose-dependent. The supernatants of MSCs derived from ALL, HD and NHL had effect on T-cell proliferation. By using neutralising monoclonal antibodies, we found that transforming growth factor beta1 (TGFbeta1) and hepatocyte growth factor were major mediators of T-cell suppression by MSCs derived from ALL, HD and NHL. Although MSCs derived from patients with myelodysplastics syndromes (MDS) could inhibit T-cell proliferation stimulated with mitogen or in MLR, the inhibitory effect of MDS-MSCs was impaired. However, adherent cells derived from patients with acute myeloid leukemia (AML) showed abnormal immunomodulatory functions. Adherent cells derived from AML failed to suppress the proliferation of T-cell stimulated in MLR.
间充质干细胞（MSCs）因其能够分化为多种间充质谱系并支持造血作用而备受关注。最近，在证实其具有免疫抑制作用后，MSCs引发了更多的研究兴趣。然而，MSCs的免疫抑制能力是否会随疾病状态而改变仍不清楚。在本研究中，我们的结果表明，来自淋巴细胞白血病（ALL）、霍奇金病（HD）和非霍奇金淋巴瘤（NHL）患者的MSCs能够抑制混合淋巴细胞反应（MLR）中受刺激的T淋巴细胞的增殖。来自ALL、HD和NHL的MSCs对T细胞增殖的免疫抑制作用呈剂量依赖性。来自ALL、HD和NHL的MSCs的上清液对T细胞增殖有影响。通过使用中和单克隆抗体，我们发现转化生长因子β1（TGFβ1）和肝细胞生长因子是ALL、HD和NHL来源的MSCs抑制T细胞的主要介质。虽然来自骨髓增生异常综合征（MDS）患者的MSCs可以抑制有丝分裂原刺激或MLR中的T细胞增殖，但MDS-MSCs的抑制作用受损。然而，来自急性髓性白血病（AML）患者的贴壁细胞表现出异常的免疫调节功能。来自AML的贴壁细胞未能抑制MLR中受刺激的T细胞的增殖。
