1995年日本学者Sakaguchi等^[1]首次证实外周血中CD4^＋T细胞中5％-10％的CD4^＋CD25^＋T细胞具有免疫抑制功能，它们能预防和阻止自身免疫病的发生发展，这群细胞被定义为CD4^＋CD25^＋调节性T细胞（regulatory T cells，Treg）。近十多年对Treg在自身免疫病发病中的作用及机制进行了深入研究，
Recent evidence indicates that mesenchymal stem cells (MSC) possess immunosuppressive properties both in vitro and in vivo. We previously demonstrated the functional abnormality of bone marrow derived MSC in patients with systemic lupus erythematosus (SLE). In this study, we aimed to investigate whether transplantation of human bone marrow derived MSC affects the autoimmune pathogenesis in MRL/lpr mice. We found that human MSC from healthy donors reduced the proliferation of T lymphocytes from MRL/lpr mice in a dose-dependent fashion. Two weeks after in vivo transfer of MSC, we detected significantly reduced serum levels of anti ds-DNA antibodies and 24 hour proteinuria in MRL/lpr mice as compared with control groups without MSC transplantation. Moreover, flow cytometric analysis revealed markedly reduced number of CD4+ T cells while increased Th1 subpopulation in MSC group and MSC + CTX group when compared with controls. Histopathological examination showed significantly reduced renal pathology in MSC-treated mice. Immunohistochemical studies further revealed reduced expression of TGF-β, FN, VEGF and the deposition of complement C3 in renal tissue after MSC and MSC + CTX treatment. Taken together, we have demonstrated that transplantation of human MSC can significantly inhibit the autoimmune progression in MRL/lpr mice.
Kangxing ZhouHuayong ZhangOuyang JinXuebing FengGenhong YaoYayi HouLingyun Sun
