Browsing by Author "Yu, Si"

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    A Retrospective Study of Conversion From Tacrolimus-based to Sirolimus-based Immunosuppression in Orthotopic Liver Transplant Recipients
    (Başkent Üniversitesi, 2008-06) Yu, Si; Huang, Jiefu; Ju, Weiqiang; Zhu,Xiaofeng; Ma, Yi; Yang, Lu; He, Xiaoshun
    Objectives: Calcineurin inhibitors are used widely in liver transplant recipients. Sirolimus is a new, potent immunosuppressant considered to be nonnephrotoxic. There is limited experience with the use of sirolimus in liver transplant recipients. This study aimed to investigate the clinical experience of conversion from tacrolimus-based to sirolimus-based immunosuppression in liver transplant recipients. Patients switched to cyclosporine-based immunosuppression during the same period were enrolled as controls. Materials and Methods: This retrospective study examined liver transplant recipients who had been switched from tacrolimus-based to sirolimus-based or cyclosporine-based immunosuppressive therapy between January 2004 and January 2007 in the first affiliated hospital of Sun Yat-sen University. Patients were divided into 3 groups: those switched to sirolimus-based immunosuppression owing to acute rejection (group SIR-AR; n=11); those switched to sirolimus-based immunosuppression owing to renal insufficiency (group SIR-RI; n=18), and those switched to cyclosporine-based immunosuppression owing to acute rejection (group CsA-AR; n=15) Results: In patients switched owing to acute rejection, the rate of successful conversion was 54.5% in group SIR-AR (6/11) compared with 60% in group CsA-AR (9/15); this difference was not statistically significant (P > .05). After conversion, renal function in patients in group SIR-AR remained normal. Conversely, renal function in patients in group CsA-AR became abnormal 3 months after conversion. In patients who were switched owing to renal insufficiency in group SIR-RI, renal function improved significantly after conversion (P < .05). In the sirolimus groups, some sirolimus-associated adverse effects occurred but were limited and well controlled. Conclusions: Sirolimus can be used safely in liver transplant recipients. In the early stages after liver transplant, sirolimus combination therapy is recommended to prevent acute rejection. For patients with tacrolimus-related adverse effects, a sirolimus-based immunosuppression regimen is a rescue therapy.
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    Tolerogenic Semimature Dendritic Cells Induce Effector T-cell Hyporesponsiveness by the Activation of Antigen-Specific CD4+ CD25+ T-Regulatory Cells
    (Başkent Üniversitesi, 2009-09) Fu, Bi-mang; Huang, Jie-fu; Tam, Nga-lei; Wu, Lin-wei; Ma, Yi; Hu, An-bin; Yu, Si; He, Xiao-shun
    Objectives: Researchers recently discovered a group of semimature dendritic cells that induce autoimmune tolerance by activating host antigen-specific CD4+CD25+ T-regulatory cells. We hypothesized that donor semimature dendritic cells injected into recipients would induce effector T-cell hyporesponsiveness by activating CD4+CD25+ T-regulatory cells. Materials and Methods: Donor myeloid semimature dendritic cells were cultivated for 6 days and were then stimulated with tumor necrosis factor α for 24 hours. BALB/c mice were pretreated with semimature dendritic cells to generate antigen-specific CD4+CD25+ T-regulatory cells in vivo. The role of CD4+CD25+ T-regulatory cells in transplant immunity was studied via mixed lymphocyte culture in vitro. Results: Surface markers and cytokines secreted by semimature dendritic cells differed from those secreted by immature myeloid dendritic cells or mature dendritic cells. Semimature dendritic cells and immature myeloid dendritic cells did not activate allogenic lymphocyte responses in coculture studies. CD4+CD25+ T-regulatory cells of recipients challenged by donor semimature dendritic cells, which expressed a high level of interleukin-10, induced hyporesponsiveness in host effector T cells that were stimulated by donor splenocytes. In contrast, CD4+CD25+ T-regulatory cells did not induce hyporesponsiveness in effector T cells when the host T cells were stimulated by third-party antigen from DBA2 mice splenocytes. Conclusions: Our findings confirm that semimature dendritic cells are an independent subgroup of dendritic cells in both immune function and morphologic profile. It may be the cytokine secretion profile of semimature dendritic cells (rather than that of surface markers) that has a key role in inducing CD4+CD25+ T-regulatory cells to express a high level of interleukin-10. Immunization with donor semimature dendritic cells may be an effective method of inducing transplant tolerance, but further evidence-based studies of that topic are necessary