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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by activation and proliferation of autoreactive T cells and B cells. We examined changes in cell cycle progression of T cells from MRL/lpr mice with or without allogenic bone marrow mesenchymal stem cells (BMMSCs) treatment and analyzed the expression of cell cycle associated proteins. In addition, the Akt/GSK3β protein kinase cascade was studied. We demonstrated that highdose MSCs transplantation effectively ameliorated disease activity in MRL/lpr mice. BMMSCs treatment inhibited G1/S transition of the abnormal lupus T lymphocytes. Moreover, it increased the expression of p21WAF1/CIP1 and p27Kip1 and decreased the expression of CDK2. Furthermore, high-dose MSCs inhibited abnormal activation of the Akt/GSK3β signaling pathway of T cells from MRL/lpr mice. Our results suggest that high-dose BMMSCs transplantation successfully treated MRL/lpr lupus mice by inhibiting abnormal activation of Akt/GSK3β signaling pathway of T cells. [ABSTRACT FROM AUTHOR]