Groh Margaret E, Maitra Basabi, Szekely Emese, Koç Omer N
Division of Hematology/Oncology, Department of Medicine, Case Comprehensive Cancer Center at Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH 44106, USA.
Exp Hematol. 2005 Aug;33(8):928-34. doi: 10.1016/j.exphem.2005.05.002.
Human bone marrow-derived mesenchymal cells (MSCs) are precursors of nonhematopoietic mesenchymal cells of the bone marrow microenvironment. MSCs were shown to inhibit alloreactive T lymphocytes, but the mechanism and mediators of this effect are not fully understood. Here we describe a novel interaction between blood monocytes and bone marrow-derived, culture-expanded MSCs, which results in inhibition of T-lymphocyte activation. We found that CD14+ monocytes from blood activate MSCs to secrete inhibitory molecules that lead to inhibition of alloreactive T cells. This cellular communication is not contact-dependent, but rather is mediated by soluble factors that include interleukin (IL)-1beta. MSC-mediated inhibition of alloreactive T lymphocytes is associated with downregulation of activation markers CD25, CD38, and CD69 detected both in CD4+ and CD8+ T lymphocytes. The cytokines secreted by MSCs that mediate T-cell inhibition include transforming growth factor-beta1, but not IL-10. The interaction between blood monocytes and the MSCs represents a unique immune regulatory paradigm that can potentially be exploited in clinic.
人骨髓间充质细胞（MSC）是骨髓微环境中非造血间充质细胞的前体。已表明MSC可抑制同种异体反应性T淋巴细胞，但其作用机制和介导因子尚未完全明确。在此，我们描述了血液单核细胞与骨髓来源、经培养扩增的MSC之间的一种新型相互作用，这种相互作用导致T淋巴细胞活化受到抑制。我们发现血液中的CD14 +单核细胞激活MSC分泌抑制性分子，从而抑制同种异体反应性T细胞。这种细胞间通讯不依赖细胞接触，而是由包括白细胞介素（IL）-1β在内的可溶性因子介导。MSC介导的对同种异体反应性T淋巴细胞的抑制作用与在CD4 +和CD8 + T淋巴细胞中检测到的活化标志物CD25、CD38和CD69的下调有关。介导T细胞抑制作用的MSC分泌的细胞因子包括转化生长因子-β1，但不包括IL-10。血液单核细胞与MSC之间的相互作用代表了一种独特的免疫调节模式，有可能在临床上加以利用。
