Effect of nonmyeloablative unrelated fetal and neonatal murine peripheral blood mononuclear cell infusion on MRL/lpr mice.

Abstract

For patients with refractory systemic lupus erythematosus (SLE), current medications are insufficient to control their condition, and new treatments are necessary. We investigated the effect of fetal and neonatal murine peripheral blood (FNPB) mononuclear cells on MRL/lpr lupus-prone mice. Female MRL/lpr mice were randomized to three groups (control, radiation and infusion groups). The infusion group had significantly better results for survival rate, body weight increase, reduction of spleen index, serum anti-ds-DNA antibody, antinuclear antibodies (ANA) and creatinine (Cr), 24 h urine protein and pathological renal tissue lesions than either the control or radiation group. Graft versus host disease (GVHD) was not observed in MRL/lpr mice in the infusion group. The infusion group also had better hematogenesis reconstruction than the radiation group. Flow cytometry analysis revealed a significant increase in Th1, CD8+ T and T reg cells and a reduction in Th2, CD4+ T and Th17 cells in the peripheral blood of the radiation and infusion groups compared with the control group. Immunocytochemical assay revealed a significant increase in serum transforming growth factor (TGF)-β and a significant reduction in interleukin (IL)-17 in the radiation and infusion groups compared with the control group. Therefore, our study showed that FNPB mononuclear cell infusion has a significant role in regulating CD4+ T cells, Th1/Th2, Th17/T reg balance and their corresponding cytokines in MRL/lpr mice. The FNPB mononuclear cell infusion provided evidence in animals and suggested a potential clinical application for umbilical cord blood transplantation to treat SLE patients.