Immuno-suppressive effects on T cells mediated by mesenchymal stem cells from patients with myelodysplastic syndrome / 中国实验血液学杂志

The study was aimed to compare the effects of T-cell suppression mediated by mesenchymal stem cells (MSC) from normal individuals and myelodysplastic syndromes (MDS) patients. MSC were cultured from the bone marrow of 12 healthy volunteers and 12 MDS patients, the morphology, surface markers and expression of several cytokines of MSC from normal individuals and MDS patients were compared, and the effects of T-cell suppression were tested in the following assays: phytohemaglutinin (PHA)-primed cultures, mixed lymphocyte reaction (MLR), cell cycle of T-cell after PHA-primed cultures and apoptosis of T-cell as well. The results showed that the MSC from normal individuals and MDS patients were similar in morphology, proliferation and surface markers. The suppressions of T-cell proliferation induced by PHA and alloantigens mediated by MDS-MSC were significantly lower than that of normal MSC. More T-cells were arrested in G0/G1 phase by normal MSC, while the effects were deficient by MDS-MSC. The suppression of T-cell activation mediated by MDS-MSC was also lower than that of normal MSC, but suppression effect on T-cell apoptosis increased. The cytokines TGF-beta1, 3, FasL expressed by MDS-MSC were reduced as compared with normal MSC, but TGF-beta2 expression increased in MDS-MSC. It is concluded that although the morphology, proliferation and cell surface markers of MDS-MSC are normal, the T-cell suppression mediated by MDS-MSC is deficient as compared with normal controls. Whether these abnormalities are relevant to the pathogenesis of aplastic anemia remains to be determined.

Effect of human bone marrow mesenchymal stem cell on allogeneic T lymphocyte phenotype in vitro / 中国实验血液学杂志

The purpose was to study the effect of mesenchymal stem cell (MSC) on immune function, and to explore the new strategy to prevent graft versus host disease (GVHD) and host versus graft reaction (HVGR) in allogeneic bone marrow transplantation. MSCs from human bone marrow cells were isolated and cultured. The purity of MSCs were identified with the spindle-fibroblastic morphological characterization by microphotography, and the phenotypes were tested by flow cytometry. MSCs were planted in 6-well plates (8 x 10(4)/well for group A, 4 x 10(4)/well for group B and 2 x 10(4)/well for group C), and cocultured for 7 days with T cell isolated from peripheral blood. Peripheral blood T cells non-cocultured with MSC acted as the control group. CD3, CD4, CD8, and CD25 expressed on T cells were analyzed by flow cytometry after coculture with MSCs for 0, 24, 72 hours and 7 days respectively. The results showed that CD4(+)CD25(+) T cells and CD8(+) T cells of allogeneic T lymphocytes cocultured with bone marrow MSCs (group A and group B) increased obviously as compared with control group (T lymphocytes uncocultured with MSCs), and there were no difference between groups A and B. CD3, CD4, CD8 and CD25 expressed on T cells had no significant difference between experimental groups and control group. The result suggested that CD4(+)CD25(+)-regulatory T cells and CD8(+) T cells were increased apparently when cocultured with allogeneic MSCs. It is concluded that MSCs pretreatment may be useful in the prevention of GVHD and HVGR in allogeneic bone marrow transplantation and provides a new strategy to induce transplantation tolerance.

The effect of MSC on cytokine production by naive T cell differentiated in vitro / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of mesenchymal stem cell (MSC) on naive T cell and to explore its mechanism of immunoregulation.</p><p><b>METHODS</b>After culturing for 3 passages, MSC was incubated with naive T cells differentiated from cord blood CD34(+) cells in vitro. Variance of cytokine produced by naive T cell in culture supernatant was analyzed by enzyme-linked immunoassays.</p><p><b>RESULTS</b>On the 7th day of co-culture, a mild proliferation of T cells in the co-culture group was observed: (9.15 +/- 0.68) x 10(5)/well in MSCs + naive T cells group versus (4.87 +/- 1.33) x 10(5)/well in naive T cells alone group (P < 0.05). IFN-gamma production was lower in MSCs + naive T cells group than that in naive T cells alone group: (1.147 +/- 0.181) pg/ml versus (4.897 +/- 0.189) pg/ml (P < 0.05), but IL-2 production was higher in the co-culture group: (16.141 +/- 2.729) pg/ml versus (2.551 +/- 0.460) pg/ml (P < 0.05). Neither IL-4 nor IL-10 were detected.</p><p><b>CONCLUSIONS</b>MSC have allogeneic effect on naive T cell, but may suppress alloreactive T lymphocyte and reduce the incidence of GVHD partly by decreased IFN-gamma production. The result may provide new clues for explaining immunoregulatory mechanism of MSC.</p>