Regulation of mesenchymal stem cells on CD4+ Foxp3+ T cells in systemic lupus erythematosus / 中华风湿病学杂志

ABSTRACT

Objective To investigate the in vivo or in vitro immune regulatory effects of allogeneic bone-marrow mesenchymal stem ceils (MSC) and human umbilical cord MSC on CD4+ Foxp3+ T cells in the peripheral blood of patients with systemic lupus erythematosus (SLE) and in the spleen of MRL/Ipr mice. Methods Human MSC were isolated and expanded from bone marrow cells of healthy donors and infused into five SLE patients. The percentages of CD4+ Foxp3+ T cells in peripheral blood were detected by flow cytometry. Human peripheral blood mononuclear cells (PBMC) were prepared by centrifugation on a Ficoll Hypaque density gradient. The MSC and PBMC from unrelated donors (MSCPBMC =11,110,150) were added into 24-well plates. After 72h of co-culture, the percentages of CD4+ Foxp3+ T cells were detected by flow cytome- try. Twenty four 18-week-old MRL/Ipr female mice were divided into 3 groups and were injected with umbilical cord MSC (1×106 cells for one time, 1×106 cells for three times and 0.5 ml sodium chloride as control respectively). The percentages of CD4+ Foxp3+ T cells in spleen and lymphoid nodes were detected by flow cytometry. Results The percentages of blood CD4+ Foxp3+ T cells at one week (4.8± 1.6)% and at three months (6.0±2.6)% post MSC transplantation for patients with SLE were both higher than that before transplantation (2.1±1.2)% (n=5,P<0.05). The co-culture of normal bone marrow MSC with PBMC from SLE patients resulted in a statistically significant increase of CD+ Foxp3+ T cells percentage in PBMC on a dose dependent manner (P<0.05). The percentages of CD4+ Foxp3+ T cells of PBMC from SLE patients co-cultured with lupus MSC were lower than that of normal MSC (P<0.05). The cultured supematant of normal MSC also upregulated the percentages of CD4+ Foxp3+ T cells of PBMC from SLE patients (P<0.05). The MRL/lpr mice that had been injected umbilical cord MSC for one time and three times had higher percentages of CD4+ Foxp3+T cells in the spleen but lower in the lymphoid nodes as compared with controls (P<0.01), but without statistical significant difference. Conclusion Allogeneic or heterogeneie MSC transplantation upregulates the percentages of CD4+ Foxp3+ T cells in SLE patients or in MRL/Ipr mice. Upregnlation of Treg population may be one of the mechanisms of MSC transplantation that is effective for SLE treatment.