树突状细胞在角膜移植免疫排斥反应中的作用

角膜移植术后的免疫排斥反应是导致手术失败的主要原因,树突状细胞在角膜移植免疫排斥反应中起着多方面作用,其作用机制成为研究热点.近年来,通过角膜移植动物模型发现,树突状细胞能够诱导不同类型的免疫反应.通过减少树突状细胞数量、抑制树突状细胞提供双信号的能力以及通过树突状细胞诱导免疫耐受等防治角膜移植免疫排斥反应的研究方法,目前取得了一定进展.     

TGF-β与角膜移植诱导的免疫耐受

角膜移植术后免疫排斥反应是角膜移植失败的主要原因.如何诱导免疫耐受是角膜移植成功的关键.许多研究表明,TGF(转化生长因子)-β不仅与角膜移植免疫耐受有密切关系,而且在其它器官移植免疫耐受中也发挥重要作用.本文就TGF-β的生物学特性及其角膜移植中TGF-β的作用作一综述.     

角膜移植免疫排斥反应防治研究进展

角膜移植术后发生免疫排斥反应是导致移植手术失败的主要原因。角膜移植与其他器官移植相比，不易发生免疫排斥反应，主要原因：前房的相关免疫偏离状态；血．房水屏障；角膜缺乏血管、淋巴组织；角膜中央区不含成熟抗原提呈细胞；房水中有大量免疫调节分子；眼前节有Fas配基表达等。角膜移植免疫排斥反应是一个复杂的反应过程，一般包括宿主对异体组织抗原的致敏和宿主对异体组织抗原的反应两方面。相应的治疗措施应围绕三方面：（1）阻断宿主对异源组织抗原的敏感性；（2）诱导免疫耐受，使淋巴不激活或活性减低；（3）降低或阻断免疫效应因素对角膜植片的破坏。随着对角膜移植排斥反应机制的深入研究，将有新的治疗措施出现，特别是诱导免疫耐受防治角膜移植排斥反应的研究前景乐观。     

角膜移植排斥反应中调节性T细胞的发展及应用

角膜移植术是角膜盲的有效治疗方式,是角膜盲患者复明的唯一希望。角膜无血管、无淋巴管,被称为免疫赦免器官,因此角膜移植术的成功率明显高于其他器官移植术,但角膜移植术后的排斥反应仍然是角膜移植术失败的主要原因。器官移植术后的免疫反应主要是免疫细胞向淋巴组织、炎症部位的定向移动,而调节性T细胞(regulatory T cells,Treg)在免疫调节中起着关键性作用,其可以通过调节和抑制效应T细胞的活化来诱导免疫耐受,从而减轻角膜移植术后的排斥反应。据此,文章对在角膜移植术后发生免疫排斥反应中Treg的来源、作用机制以及治疗等多方面做简单综述,同时也探讨了应用冬虫夏草提取物FTY720增强Treg的有效性,以期为后续针对性开展临床应用转化及基础研究提供一定的参考。     

角膜移植免疫排斥反应细胞疗法的研究进展

角膜移植术后免疫排斥反应是导致手术失败的主要原因,而临床上常用的免疫抑制剂存在着许多不良反应.细胞治疗效果确切,不良反应少,已成为新的研究热点.大量研究表明,在诱导、维持机体免疫耐受和免疫应答稳态方面具有重要作用的调节性T细胞能直接参与角膜移植术后免疫耐受的形成.近年来,树突状细胞被发现在免疫系统中扮演着双重角色,除作为抗原递呈细胞诱发免疫反应外,不成熟或表达抑制性细胞因子的树突状细胞还可诱导免疫耐受.体内外研究表明,间充质干细胞是一种具有多向分化潜能的非造血基质细胞,可通过对免疫细胞的影响,诱导抗炎效应和/或免疫耐受状态,有效抑制器官移植排斥反应.而作为继Tregs之后的又一热点细胞,髓源性抑制细胞能由多种途径抑制效应性T细胞增生,减少细胞因子的分泌,促进T细胞凋亡,抑制B细胞、NK细胞和巨噬细胞等的活动,甚至能诱导Tregs的产生,在抑制自身免疫性疾病和器官移植排斥中起着重要的作用.本文就以上4种细胞的免疫特点及其在角膜移植排斥反应治疗方面的研究进展进行综述.     

调节性T细胞在角膜移植排斥反应中的研究进展

角膜移植术是治疗终末期角膜疾病的常用方式,虽然角膜移植的成功率较其它器官移植高,但是术后排斥仍然是手术失败的主要原因。器官移植后排斥反应高度依赖于免疫细胞向淋巴组织或炎症部位的定向迁移和归巢,并受粘附分子和趋化因子的调控。调节性T细胞在免疫调节中起着关键性作用,通过诱导免疫耐受维持内环境稳定,在器官移植排斥反应、自身免疫性疾病及肿瘤相关研究中发挥重要作用。本篇综述主要介绍调节性T细胞参与眼部免疫耐受的相关研究,着重阐述调节性T细胞在角膜移植排斥过程中的作用、机制和应用。     

角膜移植免疫耐受的研究进展

排斥反应是角膜移植失败的主要原因.临床治疗中常用的非特异性免疫抑制剂,如糖皮质激素、环孢素A等,存在着许多全身副作用.因此诱导受体建立针对供体角膜的特异性免疫耐受是治疗排斥反应的理想方法.免疫耐受的机制主要包括T细胞克隆失活(anergy)、克隆清除(delete)、细胞因子介导的抑制及免疫平衡等.现就目前人工诱导免疫耐受的方法作一综述.     

穿透角膜移植术后免疫排斥反应高危因素分析

为确立角膜移植术后免疫排斥反应的有效防治策略。对穿透角膜移植术后发生免疫排斥反应的８６个病例（１００只眼）进行回顾性总结。统计分析结果表明：血管化角膜、大植片移植、植床术前的活动性炎症，偏中心移植、多次移植、联合手术均应视为穿透角膜移植术后免疫排斥反应的高危因素，而移植片上皮反复脱落、旧病复发、术眼再次手术、缝线松解与拆线等可能是诱导排斥反应发生的促发因素。结论：从分子水平减少供受体间的抗原差异，研制新一代高效安全的免疫抑制剂、创造免疫耐度的理想环境可能是控制高危角膜移植免疫排斥反应的有效防治措施。     

免疫赦免在小鼠角膜移植排斥中的作用研究

目的:阐明同种异体小鼠角膜移植术后免疫排斥反应及免疫赦免的相关性。方法:建立小鼠原位角膜移植及同种异体小鼠角膜移植实验模型。观察原位移植与同种异体移植术后角膜植片发生排斥的情况,对比两种移植术后植片的存活率,了解小鼠角膜移植术后发生排斥反应与免疫赦免反应之间的关系。结果:小鼠原位角膜移植术后植片100%存活;同种异体小鼠角膜移植术后存活率为25%。结论:小鼠角膜移植术后免疫排斥并非绝对,免疫赦免在角膜移植术中发挥重要作用。     

免疫耐受对角膜移植片长期存活的价值

穿透性角膜移植是治疗角膜盲的主要手段,尽管角膜是器官移植的免疫赦免部位,但同种异体免疫排斥反应仍是角膜移植片失败的主要原因.据统计,18%的常规角膜移植或75%的高危角膜移植患者会发生排斥反应.目前临床使用的各种免疫抑制剂主要通过作用于T淋巴细胞达到抑制免疫排斥反应的目的,但长期使用费用昂贵,且为非特异性免疫抑制.当免疫抑制剂不足时就会发生排斥反应,而抑制过强易诱发感染或肿瘤,并且阻断受体形成免疫耐受.     

Characteristics of immunotolerance induced by intratesticular injection of S-antigen

Experimental autoimmune uveoretinitis (EAU) induced by immunization of male Lewis rats with bovine S-antigen (S-Ag) is prevented by injection of S-Ag into the testis prior to immunization. This protection of animals is due to the induction of systemic immunotolerance or immunosuppression, which the authors designate orchidic tolerance. In this paper they first present a brief review of several features of orchidic tolerance reported previously and features uncovered more recently, and then propose a possible sequence of events that is initiated by antigen challenge in the testis and results in the proliferation of specific subclasses of lymphocytes with immunosuppressive activity and prevention of the onset of EAU.     

Rejection of corneal allografts

Corneal graft rejection is the major cause of penetrating keratoplasty failure. It is a complex immunological process that involves recognition of alloantigens from the corneal graft by the host's immune system, leading to an efferent immune response against the graft. Each layer of the cornea can undergo rejection, endothelial rejection being the most severe form. In some cases, rejection will lead to corneal graft failure. Many donor- and host-related risk factors contribute to corneal graft rejection. Corticosteroid therapy, topical or systemic, is the gold-standard in the preventive and curative treatment of rejection. Other immunosuppressive agents are promising but require further evaluation. Early detection of rejection is essential to establish an aggressive treatment and reduce the risk of graft failure. Prevention of rejection is also based on tissue matching between donor and recipient. In high-risk patients, ABO compatibility decreases the risk of rejection. HLA compatibility could positively influence corneal graft survival in some cases.     

Corneal graft rejection

Penetrating keratoplasty is the most widely practiced type of transplantation in humans. Irreversible immune rejection of the transplanted cornea is the major cause of human allograft failure in the intermediate and late postoperative period. This immunological process causes reversible or irreversible damage to the grafted cornea in several cases despite the use of intensive immunosuppressive therapy. Corneal graft rejection comprises a sequence of complex immune responses that involves the recognition of the foreign histocompatibility antigens of the corneal graft by the host's immune system, leading to the initiation of the immune response cascade. An efferent immune response is mounted by the host immune system against these foreign antigens culminating in rejection and graft decompensation in irreversible cases. A variety of donor- and host-related risk factors contribute to the corneal rejection episode. Epithelial rejection, chronic stromal rejection, hyperacute rejection, and endothelial rejection constitute the several different types of corneal graft rejection that might occur in isolation or in conjunction. Corneal graft failure subsequent to graft rejection remains an important cause of blindness and hence the need for developing new strategies for suppressing graft rejection is colossal. New systemic pharmacological interventions recommended in corneal transplantation need further evaluation and detailed guidelines. Two factors, prevention and management, are of significant importance among all aspects of immunological graft rejection. Preventive aspects begin with the recipient selection, spread through donor antigenic activity, and end with meticulous surgery. Prevention of corneal graft rejection lies with reduction of the donor antigenic tissue load, minimizing host and donor incompatibility by tissue matching and suppressing the host immune response. Management of corneal graft rejection consists of early detection and aggressive therapy with corticosteroids. Corticosteroid therapy, both topical and systemic, is the mainstay of management. Addition of immunosuppressive to the treatment regimen helps in quick and long term recovery. Knowledge of the immunopathogenesis of graft rejection may allow a better understanding of the immunological process thus helping in its prevention, early detection and management.     

穿透性角膜移植排斥反应危险因素分析

目的:探讨穿透性角膜移植术后植片排斥的危险因素。方法:回顾性分析我院2001-01/2008-01实施穿透性角膜移植发生排斥反应的病例,分析各因素在植片排斥反应病例中所占的比率及各种病例中植片排斥的发生率。结果:总排斥反应率为31.0%,其中普通组为25.5%,高危组为59.4%(P<0.05)。眼部化学伤排斥反应发生率最高48.1%(P<0.05)。高危组发生排斥反应早且病情严重。结论:引起角膜植片排斥的多种因素中,不同疾病的穿透性角膜移植的发生率不同,排斥反应的发生与术前原发病,植床情况,手术设计操作术后预防有密切关系,其中植床新生血管是植片排斥的高危因素。     

Risk factors for the first episode of corneal graft rejection in keratoconus

PURPOSE: To evaluate the relationship between topical corticosteroids and other variables and the risk for rejection after penetrating keratoplasty for keratoconus. METHODS: The records of all keratoconus patients who, after their first penetrating keratoplasty in that eye, experienced a first episode of corneal graft rejection during a specific 3-year period were retrospectively reviewed in a case-control fashion. Twenty-three cases were identified, and they were matched with 3 controls each, for a total of 69 controls and 92 total patients. Multiple variables including steroid potency, recent steroid tapering, and length of time on the current level of steroids were analyzed to see whether there were any significant relationships between postoperative changes in steroid management and rejection. In addition, other variables such as graft size, suture technique, recent suture removal, suture status at the time of the rejection episode, and prior grafting in the fellow eye were examined to determine if any of these factors were associated with a higher risk of graft rejection. RESULTS: Most of the proposed risk factors, including steroid dose and tapering, differing suturing techniques, loose and/or broken sutures at the time of rejection, percentage of sutures remaining at the time of rejection, and prior grafting in the fellow eye, did not correlate with the risk of rejection. Only graft size had a correlation, with host trephination size > or = 8.25 mm having a nearly sixfold increased risk of rejection (P = 0.015). Most patients (70%) were diagnosed with rejection at a scheduled office visit rather than at an emergency visit, and correspondingly, nearly one half (43%) had no symptoms when rejection was identified. There was no significant difference in final best-corrected visual acuities between the cases and controls, and 91% of the corneas that underwent rejection did not progress to graft failure, remaining centrally clear at most recent follow-up. CONCLUSION: In this study, the most important risk factor for rejection after corneal transplantation for keratoconus was the size of the graft. Physician detection of rejection is paramount, because a graft rejection episode is more often diagnosed at a scheduled office visit than at an emergency visit. Fortunately, progression to graft failure can usually be prevented if treatment is started promptly and intensively.     

Outcome of corneal transplant rejection: a 10-year study

PURPOSE: To study the incidence of graft rejection and the predictive factors for its reversibility. METHODS: It is a retrospective study of 1927 consecutive penetrating keratoplasties performed between January 1990 and January 2000 with more than 6 months follow up. A total of 224 rejection episodes were noted in 183 patients. Of these, 184 first rejection episodes were included in this study. RESULTS: The incidence of first rejection episode was 9.55%. Of patients 87% were symptomatic during the episode with vision loss being the commonest. The average time of onset of rejection was 15.25 +/- 14.4 months (median 11.7 months). In total, 53.3% of rejections occurred within 1 year after surgery. Of the patients who completed minimum 3 months follow up after the rejection episode, the rate of reversibility was 63.3%. Major predictive factors for a poor outcome after rejection were repeated grafting and associated anterior vitrectomy during surgery. The reversibility of the episode did not differ significantly with the modality of treatment used, but treatment with intravenous steroids within 7 days of onset of rejection may have a role in reducing the recurrences of rejection episodes, thus increasing the graft survival. CONCLUSION: Regrafts and associated anterior vitrectomy were significant risk factors for a poor outcome following rejection episode.     

Alpha-1--antitrypsin in aqueous humour from patients with corneal allograft rejection

PURPOSE: To investigate the presence and concentration of alpha1-antitrypsin in aqueous humour at the time of corneal rejection and to compare results obtained from patients with reversible and irreversible rejection. METHODS: Samples of aqueous humour were obtained from 17 patients with acute corneal endothelial allograft rejection. The presence of alpha1-antitrypsin in aqueous humour was confirmed by immunoblotting and measured employing a sandwich ELISA. Total protein concentrations in aqueous humour were measured using Bradford's method. The outcome of corneal rejection episodes was determined 1 month after diagnosing corneal rejection and described as reversible or irreversible rejection. RESULTS: alpha1-antitrypsin was detected in aqueous humour. Patients with reversible rejection had significantly higher alpha1-antitrypsin concentration than patients with irreversible rejection (p = 0.044). There was no significant difference in total protein concentrations (p = 0.745), and no correlation was found between alpha1-antitrypsin and total protein concentrations (p = 0.368). CONCLUSIONS: alpha1-antitrypsin in aqueous humour seems to signal a favourable outcome of corneal rejection. The possible mechanism is discussed.     

Stromal rejection in penetrating keratoplasty following COVID-19 vector vaccine (Covishield) – A case report and review of literature

Endothelial rejection has been described following both m-RNA and vector-based vaccines for COVID-19. There is one case report of a stromal rejection described following influenza vaccination. We report a case of stromal rejection following vector-based COVID-19 vaccination, which might be the first case reported so far.     

加强我国角膜移植免疫研究

通过角膜移植更换混浊或病变的角膜,是帮助角膜盲患者恢复视力的有效措施,但植片排斥反应的发生是导致角膜移植手术远期失败的主要原因,如何减少因植片排斥引起的再次致盲是角膜病研究的重点。本文分析了我国角膜移植免疫研究存在的问题：（1）没有建立标准的抗排斥治疗方案;（2）缺乏安全、有效的抗排斥反应治疗药物;（3）忽视围手术期的并发症处理;（4）角膜移植免疫基础研究薄弱。针对上述问题产生的原因,提出了相应的处理措施和建议,以增强角膜病专科医生对角膜移植免疫临床和基础研究的重视,促进我国角膜盲的防治工作取得更大的发展。     

穿透性角膜移植术后内皮型免疫排斥反应的临床研究

目的探讨穿透性角膜移植术(PKP)后内皮型免疫排斥反应发生的动态变化,及对角膜植片透明性的影响。方法对1994年1月至1998年12月在我院行PKP术并有完整记录的患者648例(648只眼),男444例(444只眼)、女204例(204只眼)进行随访,统计术后05、1、3、6、9、12、18、24、36、48个月等10个不同时间内皮型免疫排斥的发生率,以及植片混浊的发生率,比较两者动态变化的相关性,制成动态变化曲线,并对术前的病因与术后内皮型免疫排斥反应发生之间的关系进行分析。结果植片混浊与内皮型免疫排斥反应密切相关(线性相关回归分析,P<001);术后3年,内皮型免疫排斥反应的发生率仍有一定比例。术前不同病因及炎性背景的眼病,因内皮型免疫排斥反应发生率不同,而影响植片透明性。结论PKP术后,植片的透明性主要受内皮型免疫排斥反应的影响,二者密切相关;各种角膜疾病因炎性反应不同,其内皮型免疫排斥反应的发生率也不同,重视术后患者的长期随访,对维持术后角膜植片的透明性,保证手术成功率有重要意义。(中华眼科杂志,2005,41145149)