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CD4+ T cells play an important role in the progression of type 2 diabetes mellitus (T2DM).It is known that T cell responses can be suppressed by myeloid-derived suppressor cells (MDSCs).In this study,we aimed to explore the potential role of MDSCs in the progression of T2DM,and to examine whether the underlying mechanism was associated with CD4+ T cells.Peripheral blood samples were obtained from T2DM patients and healthy controls,as well as C57BL6J db/db mice and control heterozygous (db/-) mice.The frequency of MDSCs and CD4+ T cells was analyzed using flow cytometry.Serum levels of the cytokines interleukin (IL)-4,IL-10,tumor necrosis factor (TNF)-α,and interferon (IFN)-γ were quantified using ELISA kits.Cell proliferation was assessed using carboxyfluorescein succinimidyl ester (CFSE) labeling.In addition,the severity of insulitis was assessed using H&E staining of the pancreata.The data showed an increased frequency of CD11b+/CD33+ MDSCs and CD4+ T cells in the peripheral blood of T2DM patients.In addition,there were decreased IL-4 level and increased TNF-α and IFN-γ,levels in the serum from T2DM patients.In db/db mice,an increased frequency of CD11b+/Gr-1+ MDSCs and CD4+ T cells was found in splenocytes,as well as in the peripheral blood.MDSCs inhibited the proliferation and modulated the cytokine secretion of CD4+ T cells in vitro and delayed the development of diabetes in NOD/SCID mice.In conclusion,MDSCs suppress CD4+ T cell activity and prevent the development of T2DM.