Human mesenchymal stem cells require monocyte-mediated activation to suppress alloreactive T cells.
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.
Groh
Margaret E
ME
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.
Maitra
Basabi
B
Szekely
Emese
E
Koç
Omer N
ON
D015703:Antigens, CD / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015703:Antigens, CD; D016207:Cytokines