Inhibitation of T cells and dendritic cells by mesenchymal stem cells derived from the bone marrow of multiple myeloma patients / 白血病·淋巴瘤

ABSTRACT

Objective To investigate the effects of mesenchymal stem cells (MSC) derived from bone marrow of multiple myeloma patients (MM-MSC) and normal donors (ND-MSC) on the function of T cells and dendritic cells (DC). Methods MSC were isolated and cultured from bone marrow of multiple myeloma patients and normal donors. Cytokines were detected by enzyme-linked immunosorbent assay (ELISA).Immunophenotype was detected by flow cytometry (FCM). The apoptosis of cells were detected by Annexin-V/PI assay. In order to compare the influence of MSC (MM-MSC group vs ND-MSC group) on DC-mediated T cells killing function, ND-MSC (ND-MSC group) and MM-MSC (MM-MSC group) were co-cultured with DC +T cells + U266 cells, respectively. Results The expression of TGF-1 by MM-MSC were higher than that by ND-MSC (P ＜0.05). The proliferation of T lymphocytes, activation and killing function were significantly inhibited and T cells apoptosis were significantly promoted by MM-MSC than that by ND-MSC (P ＜0.05).When co-cultured with DC, MSC inhibited immature DC (imDC) maturation and IL-12 expression (P ＜0.01).After MSC co-cultured with DC + T cells + U266 cells, the apoptosis of U266 cells induced by T cells decreased significantly and the apoptosis were significantly inhibited by MM-MSC than by ND-MSC (P ＜0.01).Conclusion MM-MSC can inhibit T cell activation and killing function and express a high level TGF-1.MM-MSC may inhibit DC differentiation, maturation and cytokine secretion. MSC in bone marrow microenvironment may play an important role in pathogenesis of MM.