树突状细胞在角膜移植排斥反应中的免疫调节机制的探讨  

An investigation on the immunomodulation of dendritic cells on corneal allograft rejection

作　　者：闫峰[1] 蔡莉[2] 黄振平[1] 丁莉莉[1] 惠延年[2] 

机构地区：[1]南京军区南京总医院眼科,210002 [2]第四军医大学西京医院眼科,西安710032

出　　处：《眼科研究》2008年第10期762-765,共4页Chinese Ophthalmic Research

基　　金：国家自然科学基金(30500550);江苏省博士后科研基金(0702040C)资助

摘　　要：目的观察自体未成熟树突状细胞(iDC)对于小鼠同种异体角膜移植的免疫调节作用,探讨其作用机制。方法PBS或自体iDC尾静脉注射7d后,采用双色免疫荧光染色法及流式细胞术分析小鼠脾脏中CD4+CD28+及CD4+CTLA-4+ T细胞的表达。PBS或自体iDC尾静脉注射7d后进行小鼠同种异体角膜移植,临床观察两组植片的存活时间。结果iDC注射后,脾脏中CD4+CD28+ T细胞的比例下降(P<0.01),而CD4+CTLA-4+ T细胞比例明显升高(P<0.01)。iDC经尾静脉注射后明显延长了同种异体角膜移植片的存活时间(P<0.01)。结论iDC可诱导CD80/CD86-CTLA-4抑制型共刺激信号替代CD80/CD86-CD28信号通路,从而阻断协同刺激信号的传递及T细胞的活化,对于同种异体角膜移植排斥反应具有免疫抑制作用。Objective The aim of this paper was to study the suppression effect of syngeneic immaure dendritic cells （iDC） on corneal allograft rejection and study the action mechanisms of iDC. Methods Marrow-derived iDC were extracted from femur of Balb/c（ H -2^d） mouse and cultured in vitro. 2 × 10^6/0. 1 mL syngeneic iDC was injected into murine tail vein of Balb/c（ H -2a） mice as experimental group, and 0. 1 mL physiological balance solution （PBS） was injected as control group. The expression rates of CD4^＋ CD28 ^＋ and CD4^＋ CTLA-4^＋ T cells in splenic lymphocytes were evaluated by bicolor immunofluorescence flow cytometry in 7 days after injection. The corneal allograft transplantation was performed in 7 days after PBS or syngeneic iDC injection with the C57BL/10（H-2^b） mice corneas as donors and Balb/c（ H -2a） mice as receipients. Cornea rejection was evaluated by clinical examination. Results The positive rate of CD11 c in cultured iDC was over 70% in the fifth day and retained the immature status under the TGFβ2 stimuhion. In iDC injection group,the percentage of CD4 ^＋ CD28 ^＋ T cells in splenic lymphocytes was significantly decreased （P 〈 0.01 ） and increased in the percentage of CD4 ^＋ CTLA-4 ^＋ T ceils in splenic lymphocytes in comparison with PBS injection group （P 〈 0.01 ）. The corneal allograft rejection was delayed and the survival time of grafts was prolonged in iDC injection group compared with PBS injection group（P 〈 0. 01 ）. Conclusion iDC induce the signal activation of CD80/CD86-CTLA-4 instead of CD80/CD86-CD28 , therefore blocking CD80/CD86-CTLA-4 signaling and suppress T cells activation, which plays a role in immunosuppression of corneal allograft rejection.

关 键 词：树突状细胞 细胞毒T淋巴细胞相关分子-4 CD28 同种异体角膜移植排斥反应 免疫调节 

分 类 号：R779.65[医药卫生—眼科]