5基因工程技术诱导免疫耐受
基因治疗诱导免疫耐受有其独特优势:(1)可于移植前在体外预处理移植物,减低其毒性、免疫原性,减少载体在体内表达的可能性。(2)瞬时的目的基因表达即可改变受体的免疫状态。目前常用的载体有复制缺陷的腺病毒载体,用于基因治疗的靶分子主要有辅助分子/黏附分子、细胞因子、FasL等,并且在角膜移植模型中已有CTLA-4Ig cDNA[4]、IL-10基因[27]、FasL cDNA基因转导成功诱导免疫耐受的报道。但因为目的基因的表达效率及受体对表达基因产物的排斥反应等问题还未得到解决,限制了基因治疗的临床应用。
T细胞群中有一免疫抑制细胞亚群的存在,如CD4+CD25+T调节性细胞亚群,可抑制T细胞的活化而诱导免疫耐受,目前已有动物实验研究增强调节性T细胞的功能和数量来治疗自身免疫病和抑制移植排斥反应。目前其它器官移植实验中,有利用口服抗原、应用抑制性树突细胞诱导免疫耐受的报道。但在角膜移植中,这些方法鲜有应用。
诱导免疫耐受治疗角膜移植排斥在动物实验中已经取得了一定成果,目前的问题是如何诱导稳定持久的免疫耐受及确定已形成的免疫耐受,这是以后研究的方向。
【参考文献】 1 Li Q, Xi XH. Research development of the preventions and treatments of immunological rejection after corneal transplantation. Int J Ophthalmol(Guoji Yanke Zazhi) ,2006;6(5):1126-1129
2 Pan DY, Liu L, Liu YP. The rejection of ostrich cornea grafts in rabbits. Int J Ophthalmol(Guoji Yanke Zazhi) ,2005;5(4):649-651
3 Mandlebrot DA, Sayegh MH. Role of novel T-cell costimulatory pathways in transplantation. Curr Opin Organ Transplant ,2003;8:25-33
4 Comer RM, King WJ, Ardjomand N. Effect of administration of CTLA4-Ig as protein or cDNA on corneal allograft survival. Invest Ophthalmol Vis Sci ,2002;43(4):1095-1103
5 Kagaya F, Hori J, Kamiya K. Inhibition of murine corneal allograft rejection by treatment with antibodies to CD80 and CD86. Exp Eye Res ,2002;74(1):131-139
6 Lederman S. The role of CD154(CD40-ligand) in costimulation. Transplant Proc ,2001;33(1-2):202-206
7 Yamada AA, Sayeth MH. The CD154-CD40 costimulatory pathway in transplantation. Transplantation ,2002;73(1):36-39
8 Qian Y, Dana MR. Effect of locally administered anti-CD154 (CD40 ligand) monoclonal antibody on survival of allogeneic corneal transplants. Cornea ,2002;21(6):592-597
9 Qian Y, Boisgerault F, Benichou G. Blockade of CD40-CD154 costimulatory pathway promotes survival of allogeneic corneal transplants. Invest Ophthalmol Vis Sci ,2001;42(5):987-994
10 Safley SA, Kapp LM, Tucker-Burden C. Inhibition of cellular immune responses to encapsulated porcine islet xenografts by simultaneous blockade of two different costimulatory pathways. Transplantation ,2005;79(4):409-418
上一页 [1] [2] [3] [4] [5] 下一页 |