输注供者CD8+CD28-调节性T淋巴细胞抑制大鼠肝移植急性排斥反应的作用

目的 评价具有免疫抑制作用的CD8+CD28-调节性T淋巴细胞(Treg)体内输注在抑制大鼠肝移植急性排斥反应中的作用.方法 建立近交系大鼠肝移植自发耐受及急性排斥反应模型.从肝移植自发耐受模型受者脾脏中分离CD8+CD28-Treg,于急性排斥反应模型建立前1 d输注给受者,比较不同的输注组间受者的存活时间和移植肝病理学表现.结果 来自自发耐受模型(LEW大鼠为供者,DA大鼠为受者)的CD8+CD28-Treg输注可以延长急性排斥反应模型(LEW大鼠为供者,BN大鼠为受者)受者的存活时间,由(14.0±2.2)d延长至(24.0±3.0)d(P＜0.01),移植肝病理学显示排斥反应程度减轻.结论 大鼠肝移植自发耐受模型受者体内诱导的CD8+CD28-Treg具有抑制急性排斥反应的作用,该免疫抑制作用具有抗原特异性.     

供者骨髓细胞骨髓腔内输注联合低剂量照射延长大鼠复合组织移植物存活时间

目的探讨供者骨髓细胞骨髓腔内输注联合低剂量照射对大鼠复合组织移植物的影响。方法以SD大鼠为供者,Wistar大鼠为受者,实验分4组进行:A组仅进行肢体移植;B组在肢体移植前1d,受者接受亚致死量60Co照射(4.5Gy/次,共2次,间隔4h),同时腹腔内注射氟达拉滨(50mg/kg);C组于肢体移植当天受者骨髓腔内输注供者骨髓细胞;D组在B组的基础上,受者于肢体移植当天骨髓腔内输注供者的骨髓细胞。所有受者术后均不用免疫抑制剂。术后观察移植物的存活情况及排斥反应征象,对D组存活超过120d的受鼠进行单向混合淋巴细胞反应以及SD大鼠、DA大鼠皮肤移植,同时通过组织学检查,了解受鼠的移植物抗宿主病(GVHD)情况。结果与其它实验组相比,D组移植物的存活时间显著延长(P<0.01),达(284.2±11.8)d,未见排斥反应征象,也未观察到GVHD,其它组均于术后近期发生排斥反应(<20d);D组大鼠对供者的淋巴细胞呈现低反应性,移植的供者同系大鼠的皮肤得以长期存活,而对第三方DA大鼠的淋巴细胞和皮肤呈现强烈的免疫反应。结论供者骨髓细胞骨髓腔内输注联合低剂量照射和短期氟达拉滨应用,在不用免疫抑制剂的情况下,能显著延长移植复合组织的存活时间。     

大鼠移植肝组织中一氧化氮合酶的表达及其抑制剂的作用

目的 观察大鼠移植肝组织中一氧化氮合酶(iNOS)的表达及iNOS抑制剂氨基胍和免疫抑制剂他克莫司(FK-506)对肝移植术后急性排斥反应的影响。方法 实验分为4组：同基因组(供、受者均为LEW大鼠)；急性排斥组(供者为BN大鼠，受者为LEW大鼠)；氨基胍组、FK506组在异基因大鼠肝移植后分别应用氨基胍和FK506。用免疫组织化学法检测各组移植肝组织中iNOS表达水平。结果 急性排斥组iNOS表达呈强阳性，与氨基胍组、FK506组、同基因组比较，差异显著。结论 在大鼠原位肝移植发生急性排斥反应时，iNOS增高程度与排斥反应的强度有明显关系。氨基胍和FK506可以抑制iNOS的表达，明显减轻移植肝组织的急性排斥反应。     

1O-羟基喜树碱和环孢素A诱导异基因大鼠心脏移植受者免疫耐受的实验研究

目的以中药制剂10-羟基喜树碱(HCPT)和环孢素A(CsA)诱导异基因大鼠心脏移植受者免疫耐受,并探讨免疫耐受的特异性和形成机制.方法以纯系SD大鼠为供者,纯系Wis-tar大鼠为受者行异体颈部心脏移植.将移植后50只受者大鼠随机分成5组,分别接受不同剂量HCPT、CsA或二者联合应用.A组接受安慰剂.B组接受HCPT 1.0mg·kg-1·d-1,腹腔注射.C组接受HCPT 2.0 mg·kg-1·d-1,腹腔注射.E组接受CsA10.0 mg·kg·d-1,导管灌胃.F组联合应用HCPT和CsA,方法剂量同B组和E组.心脏移植物长期存活受者术后60 d停用免疫抑制剂,120 d同时行供者来源(SD)大鼠和无关供者(SHR)大鼠皮肤移植.结果3只C组大鼠和5只F组大鼠心脏移植术后停用免疫抑制剂长期存活超过730 d.8块SD大鼠皮肤移植物长期存活超过610 d,而8块SHR大鼠皮肤均被排斥,平均存活时间(4.50±1.25)d.结论大剂量HCPT或小剂量HCPT与CsA联合应用可诱导异基因大鼠心脏移植受者免疫耐受,且形成的免疫耐受具有明确的抗原特异性.     

小鼠自体肝脏星状细胞联合同种异体胰岛细胞移植延长移植物存活时间的研究

目的 研究小鼠自体肝脏星状细胞联合同种异体胰岛细胞移植的新方法对胰岛移植物存活时间的作用.方法 选择雄性BALB/c小鼠为胰岛移植模型的供者,雄性C57BL/6糖尿病小鼠为受者.随机将受者分为A、B两组.A组:仅采用供者的胰岛细胞移植;B组:采用受者的肝脏星状细胞(HSCs)与供者胰岛细胞混合后共同移植.术后定期测定受者尾静脉血的血糖含量.结果 B组受者胰岛移植物的存活时间明显延长,血糖含量维持正常的中位时间为66 d(30～180 d),而A组血糖含量维持正常的中位时间为11 d(9～15 d),两组比较,差异有统计学意义(P＜0.001).结论 受者肝脏星状细胞能延长共同移植的同种异体胰岛移植物存活时间.     

供肝冷缺血时间延长诱发大鼠原位肝移植术后早期急性排斥反应的研究

目的 研究供肝冷缺血时间延长对大鼠原位肝移植术后早期急性排斥反应的影响.方法 选取30只健康纯系清洁级BN大鼠和30只Lewis大鼠.分别作为纯系移植和同种异体移植的供者,受者均为健康纯系清洁级BN大鼠60只,建立纯系和同种异体原位肝移植模型.根据纯系移植和同种异体移植供肝冷缺血时间的不同,将供、受者分为A、B、C和D组,每组15对.A组:供肝冷缺血1 h后进行纯系移植;B组:供肝冷缺血18 h后进行纯系移植;C组:供肝冷缺血1 h后进行同种异体移植;D组:供肝冷缺血18 h后进行同种异体移植.术后观察受者的2周存活率、移植肝组织病理学及肝功能的改变,检测受者主要组织相容性复合物(MHC)-Ⅱ类分子和核转录因子κB(NF-κB)的表达水平.结果 肝移植术后2周,A、B、C和D组的存活率分别为83.3%、66.7%、16.7%和0%,不管是纯系移植组还是同种异体移植组中供肝的冷保存时间越短,受者的存活率越高,且经肝功能检查发现冷保存时间短的受者移植肝功能恢复较好,移植肝组织病理学损伤和急性排斥反应也明显较轻.B组受者术后移植肝大量表达MHC-Ⅱ类分子,明显高于A组(P＜0.05);两同种异体移植组MHC-Ⅱ类分子的表达量较两纯系移植组增加明显,D组增加最多.A组几乎不表达NF-κB,而B组NF-κB的表达显著增加(P＜0.05);两同种异体移植组受者NF-κB的表达峰值提前.结论 冷缺血时间的延长可以诱导发生和加重大鼠原位肝移植术后早期急性排斥反应,降低术后2周存活率.     

肝细胞胸腺内注入对大鼠异位小肠移植物的影响

目的 研究大志胸腺内注入异体抗原对异体小肠移植的影响。方法 在未用任何免疫抑制剂的情况下,将ＤＡ大鼠的肝细胞注入ＰＶＧ大鼠的胸腺内,１周后行周种异位小肠移植。结果 ３周内胸腺中注入的同种异体肝细胞存活;移植小肠遭强烈排斥,受者死亡,但胸腺内注入同一供者的肝细胞仍存活。结论 胸腺内注入同种异体肝细胞不能诱导受者对同一供者小肠移植物的免疫耐受。     

灵长类动物预致敏后肾移植加速排斥反应模型的建立

目的 建立灵长类动物预致敏后肾移植加速排斥反应模型.方法 取血型相容的正常猕猴配对,预先将供者腹部全层皮肤移植到受者背部,使受者预致敏.2周后再将同一供者的左侧肾脏移植到受者腹腔内,间时切除受者自体双肾,术后予以环孢素A、霉酚酸酯和泼尼松治疗(致敏用药组),不用免疫抑制剂者为对照(致敏对照组),以未致敏的肾移植作为对照组.术后观察受者血肌酐变化、移植物存活时间及病理特点.结果 对照组的4只移植肾存活时间分别为9、18、8、7 d;致敏对照组的3只移植肾存活时间分别为3、3、4 d;致敏用药组的3只移植肾存活时间分别为2、3、4 d.移植皮肤于术后10 d出现排斥反应,至术后14 d被完全排斥.对照组于肾移植1周以后才发牛排斥反应,而致敏者均在肾移植后3 d左右发生较严重的排斥反应.结论 受者被供者皮肤预致敏后再行肾移植,可以加速移植物的排斥,且不能被环孢素A、霉酚酸酯及泼尼松所组成的三联免疫抑制方案逆转.     

近交系大鼠腹部游离皮瓣移植模型的建立及意义

目的:为异体复合组织移植及皮肤移植免疫学研究建立一种可靠、简便而实用的动物模型。方法:以近交系Brown Norway(RT1n)大鼠为供体,Lewis(RT11)大鼠为受体,以股动静脉为血管蒂,进行腹部游离皮瓣异体移植。实验分为2组:急性排斥组(A组)术后不予免疫抑制治疗;免疫抑制组(B组)术后腹腔注射CsA剂量为20mg/kg/天。术后观察移植皮瓣的排斥情况和皮瓣存活时间,并进行组织病理学检查,以此对动物模型的可靠性和实用性进行评价。结果:A组移植皮瓣均在术后(7±1)天发生明显的逐渐加重的急性免疫排斥反应;B组移植皮瓣均可良好存活,存活时间均>100天。组织病理学检查,A组皮瓣有血管炎、毛囊炎及真皮炎症等典型急性排斥反应表现;B组皮瓣均无明显免疫排斥病理学表现。术后IL-2水平与皮瓣表面及病理学检查所见排斥反应程度相一致。结论:近交系大鼠腹部游离皮瓣移植模型是操作更为简易的血管化皮肤移植模型,其免疫排斥的发生易于观察并可稳定控制,是异体皮肤移植免疫学研究的良好动物模型。     

肝硬化大鼠原位肝移植模型的制作及术后排斥反应的观察

目的 制备肝硬化大鼠的原位肝移植模型,观察术后排斥反应发生情况,为进行其它研究创建一个平台.方法 以皮下注射CCl4联合饮用苯巴比妥钠和乙醇溶液的方法制备大鼠肝硬化模型,应用改良的"二袖套"法建立大鼠原位肝移植模型,同系移植者的供、受者均为SD大鼠(SD实验组),以接受肝移植的正常SD大鼠为对照(SD对照组);同种移植者的供者为Lewis大鼠,受者为BN大鼠(BN实验组),以接受肝移植的正常BN大鼠为对照(BN对照组).术后观察受者的存活情况以及移植肝的组织学变化.结果 肝硬化大鼠门静脉压力为(182.0±10.7)mm H2O,显著高于正常大鼠的(70.8±5.5)mm H2O(P＜0.01),移植后7 d降至(82.7±10.7)mm H2O.同种移植组术后5～12 d,移植肝组织中均可见中、重度急性排斥反应病理改变.同系移植者存活时间中位数均＞100 d;同种移植者中,BN对照组和BN实验组受者肝移植后存活时间中位数均为10 d.结论 以Lewis大鼠为供者、肝硬化BN大鼠为受者制备的肝移植模型术后排斥反应的发生率较高,可作为肝移植后排斥反应相关研究的平台.     

异体复合组织移植皮肤淋巴引流隔绝动物模型的建立

目的:通过SD大鼠下腹部游离皮瓣及皮管的移植,建立大鼠异体复合组织移植皮肤淋巴引流隔绝模型。方法:7～8周龄雄性SD大鼠切取下腹部皮瓣并游离行同种异体移植,皮肤隔离组(A组):将供体皮瓣边缘对合、缝合成管状,底边留血管蒂出口用隔离器隔离皮肤,显微外科吻合血管,皮管缝合于隔离器,隔离器固定于受体;皮肤未隔离组(B组):将供体游离皮瓣卷制成管状,显微外科吻合血管并将供受体皮肤对位缝合;空白对照组(C组):行下腹部游离皮瓣异体移植。大体观察每组皮瓣或皮管存活时间,于术后3、5、7、14、28、35d取移植物皮肤组织行HE染色,观察病理学变化。结果:A组:皮管存活时间为32(34,32)天;B组:皮管存活时间为15(16,15)天;C组:皮瓣存活时间为6(7,6)天。A组与C组、B组与C组、A组与B组存活率差异均有统计学意义(P<0.05)。结论:本实验成功建立了大鼠的异体复合组织移植淋巴引流隔绝模型,并证实了隔绝皮肤淋巴引流能有效延长移植物的存活时间。     

FK506和RS-61443对大鼠异体肢体移植的联合免疫抑制作用

目的　通过大鼠异体肢体移植模型 ,旨在分析 FK5 0 6和 RS- 6 14 4 3对大鼠异体肢体移植中急性排斥反应的免疫抑制作用。　方法　选择雄性 Wistar和 SD大鼠为供、受体 ,以 FK5 0 6和 RS- 6 14 4 3为免疫抑制剂 ,对照组为术后不用药组 ,实验组根据用药剂量和药物不同分为 6组 ,各组用药时间均为 5周 (每日 1次共 2周 ,然后每周 2次共 3周 ) ,进行了 10 1例异体肢体移植动物实验。观察大鼠一般情况、移植肢体排斥反应及存活时间。　结果　对照组肢体平均存活时间为 (7.0 0± 0 .78)天 ;实验组 1～ 6组移植肢体平均存活时间分别为 (17.0 8± 4 .5 0、2 3.2 0± 5 .0 5、11.19±2 .2 8、16 .33± 1.83、13.33± 3.2 2和 5 8.76± 6 .81)天。　结论　 FK5 0 6和 RS- 6 14 4 3能抑制大鼠同种异体肢体移植术后急性移植排斥反应的发生 ,并能延长移植肢体的存活时间。     

Rejection of islets versus immediately vascularized pancreatic allografts: a quantitative comparison

It has been suggested that free grafts of islets are rejected more vigorously than immediately vascularized intact organs grafts. However, the physiological manifestations of rejection depend, in part, upon the functional reserve of the transplanted tissue. If the number of islets transplanted is just adequate to maintain normoglycemia, the immune destruction of only a few islets will be manifested by hyperglycemia. Thus, differences in rejection time could be an artifact of the islet mass transplanted. We compared the onset of rejection of immediately vascularized segmental pancreatic grafts and of free grafts of islets under conditions in which the β cell mass transplanted, as determined by tissue insulin content, was equivalent. Lewis rats, made diabetic (plasma glucose > 400 mg/dl) by streptozotocin, received either free islet allografts by portal embolization or vascularized segmental pancreatic allografts derived from Fischer donors. Identical pancreatic segments that were not transplanted had a mean (± SE) total tissue insulin content of 33 ± 3 μg. The mean total insulin content of Fischer islets prepared by collagenase digestion in a quantity identical to that used for transplantation to single recipients was 35 ± 7 μg. Similar measurements were made in Fischer to Fischer and Lewis to Lewis isograft control groups. Recipients of both segmental pancreas and free islet grafts became normoglycemic after transplantation and this state was sustained indefinitely in recipients of syngeneic grafts. In rats receiving allografts, the day of rejection, defined as an elevation of plasma glucose to >200 mg/dl, occurred at a mean of 12.1 ± 0.3 days for recipients of pancreatic grafts (n = 17) and 5.2 ± 0.3 days in recipients of islet grafts (n = 17) (P < 0.001). The functional survival of free grafts of allogeneic islets is less than that of islets contained within immediately vascularized pancreatic grafts, even when the transplanted β cell mass is equivalent. However, this difference could still be due to nonimmunologic, quantitative factors that influenced the rate with which hyperglycemia occurred after initiation of the rejection process. The insulin content in the livers of islet isograft recipients showed that only 53 to 71% of the transplanted islets survived. Further experiments that compensate for this factor are needed to determine whether or not there are differences in susceptibility to rejection of the two types of grafts. Nevertheless, on the basis of the number of donors used per recipient, islet allotransplantation is less efficient than pancreas allotransplantation.     

Assessment of peripheral tolerance in anti-CD4 treated C57BL/6 mouse heart transplants recipients.

The study was designed to compare second heart and skin grafts and in vitro assays as a means of assessing peripheral tolerance in C57BL/6 mice. Vascularized heterotopic BALB/c hearts were placed in C57BL/6 recipients treated with anti-CD4, GK1.5 (1 mg total per 20 g mouse i.p. on days 0, 1, 2, 3). Those mice in which hearts survived for >60 days were challenged with donor and third-party (CBA) skin grafts or with second heart grafts, of donor or third-party origin, attached to the carotid artery and jugular vein. In vitro alloreactivity was assessed by mixed lymphocyte reactions (MLR) and cell mediated lympholysis (CML) using recipient spleen cells. Parenchymal damage, cellular infiltration and vascular disease were assessed from the histology of long-term allografts and isografts. Allografts in untreated recipients were rapidly rejected while isografts survived > 100 days. Primary allografts in anti-CD4 treated recipients also survived > 100 days, as did donor strain secondary heart transplants given at >60 days after the first graft. Third-party hearts were rapidly rejected, as were donor and third-party skin grafts placed on recipients with long-term allografts. These recipients showed low MLR response to both donor and third-party stimulators and donor-specific suppression of CML at 60 days post graft. Long-surviving heart allografts all showed evidence of parenchymal damage and vascular intimal thickening. Thus in the BALB/c to C57BL/6 donor-recipient strain combination, hearts, but not skin grafts, could be used to demonstrate peripheral tolerance, which seemed to be both organ and major histocompatibility complex (MHC) specific. Despite long survival, BALB/c hearts all showed evidence of parenchymal damage and vascular intimal thickening, a sign of chronic rejection.     

A new rat model to study the correlation of cardiac and skeletal muscle allograft rejection

As a first step to study the correlation of cardiac and skeletal muscle allograft rejection, we describe a new experimental rat model of simultaneous heterotopic heart and cutaneous maximus muscle flap allotransplant. Brown Norway rats were used as donors and Lewis rats as recipients. No immunosuppression was given. The grafts were revascularized with sequential end-to-side anastomosis of each vascular pedicle to the infrarenal aorta and vena cava. Syngeneic heart and cutaneous maximus muscle grafts remained functional and showed no sign of rejection at 7 days after the transplant. In contrast, both allografts developed severe rejection and functional compromise at 7 days after the transplant. Our experimental model is technically feasible and reproducible and may provide important information about the pattern of rejection of cardiac and skeletal muscle allografts. © 1998 Wiley-Liss, Inc. MICROSURGERY 18:406–409, 1998     

Prevention of obliterative airway disease in HLA-A2-transgenic tracheal allografts by neutralization of tumor necrosis factor.

BACKGROUND: Inflammatory cytokines play an important role in the development of experimental obliterative airway disease (OAD) after transplantation. To further determine the immunologic mechanisms associated with OAD development, we used a murine tracheal transplant model in which a single mismatched HLA-A2-transgenic molecule is indirectly recognized by the recipient CD4+ T cells and then determined whether neutralization of several inflammatory cytokines affected the development of OAD. METHODS: Tracheas from HLA-A2+ C57BL/6 mice were heterotopically transplanted into C57BL/6 mice. Recipients were treated with neutralizing antibodies against tumor necrosis factor (TNF), interferon-gamma (IFN-gamma), or interleukin-1 (IL-1). Allograft histology as well as anti-HLA-A2 antibody development and T cell proliferative responses were determined at days +5, +15, +28, and +60. RESULTS: Allografts in untreated and anti-IFN-gamma-treated recipients demonstrated full development of OAD by day +28. Allografts in anti-TNF-treated recipients showed no evidence of OAD, even at day +60. Allografts in anti-IL-1-treated recipients showed airway epithelium changes by day +28 but minimal evidence of OAD by day +60. Spleen cells from untreated and anti-IFN-gamma-treated recipients showed significantly higher proliferative responses to HLA-A2+ cells, compared with syngeneic recipients (negative controls). In contrast, anti-TNF and anti-IL-1-treated recipients showed significantly lower proliferative responses to HLA-A2+ cells, compared with untreated recipients. Development of anti-HLA-A2 antibodies was detected in all recipients by day +15, with the exception of those treated with anti-TNF. CONCLUSION: Among the inflammatory cytokines, TNF seems to play a crucial role in the immunopathology of OAD developed after transplantation.     

T lymphocytes mediate leaflet destruction and allograft aortic valve failure in rats

BACKGROUND: Allograft heart valves are commonly used in cardiac surgery but ultimately fail. This situation is most acute in children. This study addresses the role of T cell-mediated immune damage in allograft valve failure. METHODS: Syngeneic (Lewis to Lewis) or allogeneic (Brown Norway to Lewis) aortic valve grafts were implanted infrarenally into Lewis rat recipients (n = 24). Allogeneic valve grafts were also implanted into T cell-deficient rats (nude; n = 12). At 7, 14, and 28 days the valves were explanted and examined for structural integrity and cellular infiltration. RESULTS: Syngeneic grafts maintained normal leaflet structure with little leaflet immune infiltration. Allografts showed leaflet infiltration (7 days), significant leaflet thickening, progressively decreased cellularity (14 days), and leaflet destruction (28 days). Infiltrates contained CD43+, CD3+, and CD8+ cells. Allografts in T cell-deficient rats showed none of the above changes and maintained normal structural integrity. CONCLUSIONS: Allograft heart valves in the rat model undergo T cell-mediated immune rejection, resulting in structural failure.     

Pectoral skin flap as a reliable and simple model for vascularized composite skin transplantation research

In this study, the authors explored the feasibility of transplanting a "pectoral skin flap" as an alternative model for composite skin allotransplantation research. Genetically inbred male Lewis rats (LEW; RT1l) (n = 13), weighing 250 to 300 gr, were used as recipients and Brown Norway rats (BN; RT1n) (n = 8) rats were used as donors. Five Brown Norway rats had bilateral and three had unilateral flap harvest with a total of 13 flap transplantations to Lewis rats. All flaps were transplanted to the groin regions of the recipients and microsurgical anastomoses with 10-0 nylon were performed between the axillary vessels of the flaps and the femoral vessels of the recipient animals. The mean operation time was 55 min, with an ischemia time of 25 min. All transplantations were successful immediately postoperatively. The recipient animals were treated with Cyclosporine A (16 mg/kg/day) from the day of the surgery for 1 week, and then discontinued. One flap developed infection at postoperative day 11 and one flap had partial (50 percent) necrosis. The early signs of rejection started 8 to 9 days after the cessation of the immunosuppressive treatment, and all flaps were acutely and uniformly rejected within 3 to 4 days. The feasibility of harvesting two flaps from one donor animal allowed saving donor animal lives and reducing donor-specific variables.     

Cyclosporine mitigates graft coronary artery disease in murine cardiac allografts: description and validation of a novel fully allogeneic model.

BACKGROUND: The effect of cyclosporine (CsA) on the development of graft coronary artery disease (GCAD) is controversial. We developed a novel allogeneic mouse model of heart transplantation and investigated the effect of CsA on acute rejection and GCAD. METHODS: Hearts of FVB mice (H-2(q)) were heterotopically transplanted into 60 C57BL/6 mice (H-2(b)). CsA was administered to recipients at 10, 20 or 30 mg/kg/day for 10 or 30 days after transplantation. Untreated recipients as well as isograft recipients served as controls. Viability of the grafts was assessed daily by palpation. Parenchymal rejection was scored in grafts surviving 30 days in the 30-day treatment groups. GCAD was evaluated by the percentage of luminal narrowing, intima/media ratio and percentage of diseased vessels. Blood CsA and creatinine levels were also evaluated. Results were evaluated statistically. RESULTS: All groups except the untreated control group and the allograft groups treated with 10 or 20 mg for 10 days showed significant graft survival (>/=33% survival for 30 days). An inverse correlation was observed between CsA treatment dose, parenchymal rejection score and degree of GCAD in the 30-day treatment groups. However, graft survival in the 20-mg/kg/day group was significantly better than that in the 30-mg/kg/day group. Serum creatine levels showed no nephrotoxicity. CONCLUSIONS: Relatively high-dose CsA mitigated parenchymal rejection and GCAD of the mouse cardiac allografts. In addition, a valuable mouse model mimicking the clinical course of GCAD was achieved with CsA treatment of 20 mg/kg/day for 30 days.