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学科主题: 临床医学
题名:
Cyclosporine Combined With Nonlytic Interleukin 2/Fc Fusion Protein Improves Immune Response to Hepatitis B Vaccination in a Mouse Skin Transplantation Model
作者: Li, Z.1; Zhang, D.2; Gao, J.1; Li, W-X.1; Zhu, J-Y.1
刊名: TRANSPLANTATION PROCEEDINGS
发表日期: 2013-07-01
DOI: 10.1016/j.transproceed.2013.02.123
卷: 45, 期:6, 页:2559-2564
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Immunology ; Surgery ; Transplantation
研究领域[WOS]: Immunology ; Surgery ; Transplantation
关键词[WOS]: FOLLICULAR-HELPER-CELLS ; LIVER-TRANSPLANTATION ; SURFACE-ANTIGEN ; IN-VITRO ; T-CELLS ; TOLERANCE ; IL-2 ; DIFFERENTIATION ; FAILURE
英文摘要:

Background. Improving immune responses to vaccination in immunosuppressed patients is extremely important. Previously, we observed that cyclosporine (CsA) combined with a nonlytic interleukin (IL)-2/fragment crystallizable (Fc) fusion protein induces immune tolerance to mouse skin transplantations. In the present study, we asked whether this combination improved hepatitis B (HBV) vaccine efficacy in immunosuppressed mice while also prolonging skin graft survival.

Methods. After C57BL/6 mice received DBA/2 skin grafts, they were administered a 14-day course of CsA (30 mg/kg intraperitoneal) combined with IL-2/Fc (1 mu g, intraperitoneal). HBV vaccine (2 mu g) was injected intramuscularly on the day of skin transplantation. On day 14, the serum levels of hepatitis B surface antibody (HBsAb), IL-4, IL-10, interferon (IFN-gamma), and IL-2 were measured by enzyme-linked immunosorbent assay. We assessed the percentages of CD4(+)CXCR5(+) follicular T helper cells, CD4(+)FoxP3(+) regulatory T cells (Treg) and expressions of IL-17, IL-21, FoxP3, Bcl-6 in the spleen. Animals were divided into four groups: control, vaccine-treated, CsA vaccine-treated, CsA + IL-2/Fc + vaccine-treated hosts.

Results. Combination therapy significantly increased HBsAb levels and also prolonged skin graft survival. Serum levels of Th1 cytokines IL-2 and IFN-gamma were significantly higher in the combination group, while Th2 cytokines, IL-4 and IL-10 were lower. Combined treatment increased the percentage of Treg and the expression of Foxp3 and IL-21, meanwhile inhibiting the expression of Bcl-6. But the percentage of Tfh did not significantly change among the groups.

Conclusions. These observations suggested that a combination of CsA and IL-2/Fc fusion protein enhanced immune responses after HBV vaccination and prolonged skin graft survival.

语种: 英语
所属项目编号: 2009CB522403
项目资助者: National Basic Research Program of China (973 Program)
WOS记录号: WOS:000323852000087
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/60263
Appears in Collections:北京大学第二临床医学院_肝胆外科_期刊论文

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作者单位: 1.Peking Univ, Ctr Transplantat, Peoples Hosp, Dept Hepatobiliary Surg, Beijing 100044, Peoples R China
2.Beijing Friendship Hosp, Dept Liver Dis Inst, Beijing, Peoples R China

Recommended Citation:
Li, Z.,Zhang, D.,Gao, J.,et al. Cyclosporine Combined With Nonlytic Interleukin 2/Fc Fusion Protein Improves Immune Response to Hepatitis B Vaccination in a Mouse Skin Transplantation Model[J]. TRANSPLANTATION PROCEEDINGS,2013,45(6):2559-2564.
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