标题：Thalidomide ameliorate graft chronic rejection in an allogenic kidney transplant model
作者：Zhang, Yan; Yang, Yu; Li, Xianduo; Chen, Dongdong; Tang, Guanbao; Men, Tongyi
作者机构：[Zhang, Yan; Yang, Yu; Li, Xianduo; Chen, Dongdong; Tang, Guanbao; Men, Tongyi] Shandong Univ, Qianfoshan Hosp, Dept Urol, Jinan, Shandong, Peoples R 更多
通讯作者地址：[Men, TY]Shandong Univ, Qianfoshan Hosp, Dept Urol T, 16766 Jingshi Rd, Jinan, Shandong, Peoples R China.
关键词：Thalidomide; Chronic rejection; T cell mediated rejection; Kidney; transplantation; Treg; Th17 cell
摘要：Chronic T cell mediated rejection (TCMR), which is characterized by infiltration of the interstitium by T cells and macrophages, still remains a major barrier to the long-term survival of kidney transplantation. Our recent report indicated that thalidomide can attenuate graft arteriosclerosis in an aortic transplant model. In this study, we investigated the effect of thalidomide on chronic TCMR in a rat model of kidney transplantation.; Fischer or Lewis kidney allografts were transplanted into Lewis recipient rats. After kidney transplantation, recipient rats were divided into 3 groups: the isograft (Iso) group, allograft (Allo) group, and thalidomide (Tha) group. Rats were sacrificed at 8 weeks after kidney transplantation, and blood and kidney samples were collected. Serum concentrations of creatinine (SCr),interleukin (IL)-2, IL-6, IL-17, and TNF-a in recipients were determined, and flow cytometry was used to detect the percentages of CD4(+) CD25(+), CD4(+) Foxp3(+) and CD4(+) Th17(+) cell subsets in the peripheral blood. Grafts were procured for histopathological examination, and the expressions of a-SMA, transforming growth-beta 1 (TGF-beta 1), and VEGF in kidney grafts were investigated using Western blot. Thalidomide treatment significantly ameliorated chronic rejection, reduced renal allograft tissue damage, and decreased serum creatinine levels. Attenuation of chronic TCMR was due to the prohibited production of inflammatory cytokines, altered distribution of the CD4(+) CD25(+) FoxP3(+) regulatory T (Treg) and CD4(+) Th17(+) cells in the peripheral blood, and decreased expression of TGF-beta 1, alpha-SMA, and VEGF in the kidney graft. These results demonstrated that thalidomide could effectively ameliorate chronic TCMR in a rat kidney transplant model.