异体肢体移植中树突状细胞与免疫耐受

异体肢体移植手术的成功，使人们更关注免疫耐受的研究。树突状细胞作为耐受原可以从多个方面诱导耐受，因此日益受到人们的重视，本文综述了近年来肢体移植中树突状细胞与免疫耐受的研究进展。     

大鼠T细胞疫苗的制备及其抗移植皮肤排斥作用的实验研究

目的 探讨T细胞疫苗(TCV)的制备方法及其抗移植皮肤排斥反应的作用.方法 制备针对特定SD大鼠的供体特异性T细胞疫苗,将其免疫受体Wistar大鼠;然后取免疫前和每次免疫后第五天的受体Wistar的淋巴细胞(反应细胞)与供体SD的淋巴细胞(刺激)进行体外单向混合淋巴细胞反应(MLR),以MTT法检测细胞免疫增值反应情况,比较疫苗接种后诱导淋巴细胞反应受抑制的情况:再将SD大鼠皮肤移植到TCV免疫后的Wistar大鼠,观察皮肤移植反应并统计移植物存活的时间.排斥反应的移植物行病理检查.结果 TCV组受体淋巴细胞反应程度比接种前显著减弱(P＜0.05);特异性TCV组皮肤移植物存活时间较非特异性TCV组及对照组延长(P＜0.05).移植皮肤排斥反应病理表现更轻.结论 TCV经腹腔接种可以诱导出针对同种抗原特异性免疫耐受,TCV能够延长同种异体移植皮肤的存活时间,有一定抗移植排斥反应作用.     

CD80mAb协同imDC诱导同种异体大鼠胰十二指肠移植免疫耐受

目的 观察共刺激分子阻断剂CD80单克隆抗体（CD80mAb）在协同未成熟树突细胞（imDC）诱导同种异体大鼠胰十二指肠移植免疫耐受中的作用。方法 建立糖尿病大鼠胰十二指肠移植动物模型；4E5杂交瘤细胞株BABIMC小鼠腹腔注射，抽取腹水，分离纯化后获得CD80mAb；分离供体大鼠骨髓来源DC细胞前体，经GM—CSF、IL-4体外刺激后。再加入IL-10共培养，鉴定为imDC；移植前7d，将2×10^6imDC经静脉途径注射至受体体内，同时分别给予生理盐水1ml、CD80mAb5mg连续14d。结果 四组受体大鼠移植后中位生存时间分别为12．7d、32．4d、50．2d、92．0d，实验组存活时间明显延长；组织学观察发现移植后7dCD80mAb＋imDC组移植物形态尚完整，淋巴细胞浸润减少；混合淋巴细胞反应证实移植后7dCD80mAb＋imDC组供受体间呈低反应性。结论 共刺激分子阻断剂CD80mAb能够协同imDC诱导受体T细胞对移植物的免疫耐受，降低宿主对移植物的急、慢性排斥反应，延长移植物的存活时间。     

CD4+CD25+调节性T细胞对同种胰岛移植免疫耐受的影响

目的 观察体外分离的CD4+CD25+调节性T细胞对同种胰岛移植免疫耐受的影响.方法 免疫磁珠法分离CD4+CD25+调节性T细胞,体外试验观察其对CD4+CD25-T细胞增殖的影响.将数量达1×106的CD4+CD25+调节性T细胞回输胰岛移植受体,对比其对移植物存活的影响.结果 分离的CD4+CD25+调节性T细胞体外试验可明显抑制CD4+CD25-T细胞的增殖.单纯胰岛移植组移植物物存活期为(5.57±0.79)d,回输受体CD4+CD25+调节性T细胞数量1×106、2×106时,胰岛移植物存活时间分别为(15.29±2.29)d和(25.43±2.30)d(P《0.01).CD4+CD25+调节性T细胞回输胰岛移植受体可显著延长移植物存活期,诱导免疫耐受的作用为剂量依赖性.结论 CD+CD25+调节性T细胞体外、体内试验可抑制效应性T细胞功能,诱导胰岛移植免疫耐受.     

同种异体反应性淋巴细胞克隆疫苗回输诱导受体特异性免疫耐受的研究

目的：探讨同种异体移植抗原抗原特异性免疫耐受诱导的新途径，以达到心肺移植长期存活的目的。方法：以同种异体反应性淋巴细胞克隆在体外培养条件下大量增殖后，作为自身独特性疫苗，体内注射免疫家兔，以混合淋巴细胞反应来观察免疫前和免疫后对供体淋巴细胞刺激指数（SI）的变化。结果：同种异体反应性自身独特型淋巴细胞疫苗具有显著诱导特异性免疫应答移植现象，SI值显著降低（P＜0．05），而对卡介苗诱导的特异性免疫应答并未因独特型淋巴细胞疫苗的应用而下降，结论：同种异体反应性自身独特型淋巴细胞疫苗有可能成为诱导抗原特异性免疫耐受的一种手段。     

胸腺修饰诱导同种异体静脉移植的免疫耐受研究

目的 观察大鼠胸腺内注射异基因抗原在同种异体异基因股静脉移植免疫耐受中的作用.方法 将48只SD大鼠随机分为4组:自体股静脉移植组(A组)、异体股静脉移植组(B组)、异体股静脉移植免疫抑制剂组(C组)、胸腺内注射供体组织相容性(MHC)抗原后移植组(D组).于2周后进行影像学、组织学、免疫学检测.结果 组织学检测结果显示:D组、C组急性排斥反应损伤较轻,B组血管壁的各层结构破坏最重,可见大量炎性细胞浸润.B组受体大鼠血清干扰素(IFN)-γ浓度为(86.707±10.928)ng/L,显著高于A、C、D组[(29.328±4.170)、(69.076±8.059)、(63.355±4.895)ng/L,P<0.05];B组受体大鼠血清白细胞介素(IL)-4浓度为(23.656±3.369)ng/L,显著低于C、D组[(29.425±4.174)、(31.000±4.659)ng/L,P<0.05].结论 胸腺内注射异基因MHC抗原可诱导大鼠对同种异体血管移植的特异性免疫耐受.     

小鼠异体Sertoli细胞诱导胰岛移植免疫耐受的作用

目的 观察小鼠Sertoli细胞是否能在异体内起到诱导局部免疫耐受、保护共移植异体胰岛的作用.方法 以糖尿病C57小鼠作移植受体,随机分4组,每组6只;以正常BALB/C小鼠为胰岛供体,正常C57小鼠和正常BALB/C小鼠各作为Serloli细胞供体.A组:单纯移植异体胰岛;B组:移植来源于C57小鼠的Sertoli细胞+BALB/C小鼠来源的胰岛;C组:移植均来源于BALB/C小鼠的Sertoli细胞及胰岛;D组:假手术组.监测各组移植受体的血糖尿糖变化,观察移植物的存活时间.结果 A组移植物平均存活时间为(6.50±2.35)d;B组为(55.67±4.84)d;C组为(51.33±5.05)d;D组未观察到血糖正常.B组及C组的移植方式均可逆转糖尿病小鼠的高血糖状态,移植物存活期均较A组有明显延长,其差异有统计学意义(P<0.05);而B组与C组的移植物存活时间差异无统计学意义(P>0.05).结论 同种异体来源的睾丸Sertoli细胞在异体内可起到诱导局部免疫耐受的效果,对共移植同种异体胰岛起到保护作用,其效果与自体睾丸Sertoli细胞相当.     

胸腺修饰诱导同种异体静脉移植的免疫耐受研究

Objective To investigate the possibility of inducing immune tolerance to vein trans-plantation in rats by intrathymic injection of allogene. Methods MHC antigen extracted from splenic cells of donor Wistar rats was intrathymically injected to recipients SD rats, and donor Wistar femur vein was transplanted after 2 weeks. Forty-eight SD rats were randomly divided into 4 groups: group A ( femur vein autograft) ,group B ( femur vein allograft) ,group C ( femur vein allograft with use of immunosuppressant), group D (intrathymus injection). Imaging, histology and immunological assays of these groups were carried out 2 weeks after the transplantation. Results Histologic parameters that were tested were better in group D than those in group B. The concentration of serum IFN-γ in group B was significantly higher than that in groups A, C and D [ ( 86. 707±10.928 ) ng/L vs (29.328±4. 170), (69.076±8.059) and (63.355± 4.895) ng/L respectively, P < 0.05 ]. The concentration of serum IL-4 in group B was obviously lower than in groups C and D [ (23.656±3.369) ng/L vs (29.425±4.174) and ( 31.000±4.659) ng/L re-spectively,P < 0.05 ]. Conclusion Intrathymus injection of allogenic antigen might induce specific im-mune tolerance to femur vein transplantation in rats.     

胸腺修饰诱导同种异体静脉移植的免疫耐受研究

Objective To investigate the possibility of inducing immune tolerance to vein trans-plantation in rats by intrathymic injection of allogene. Methods MHC antigen extracted from splenic cells of donor Wistar rats was intrathymically injected to recipients SD rats, and donor Wistar femur vein was transplanted after 2 weeks. Forty-eight SD rats were randomly divided into 4 groups: group A ( femur vein autograft) ,group B ( femur vein allograft) ,group C ( femur vein allograft with use of immunosuppressant), group D (intrathymus injection). Imaging, histology and immunological assays of these groups were carried out 2 weeks after the transplantation. Results Histologic parameters that were tested were better in group D than those in group B. The concentration of serum IFN-γ in group B was significantly higher than that in groups A, C and D [ ( 86. 707±10.928 ) ng/L vs (29.328±4. 170), (69.076±8.059) and (63.355± 4.895) ng/L respectively, P < 0.05 ]. The concentration of serum IL-4 in group B was obviously lower than in groups C and D [ (23.656±3.369) ng/L vs (29.425±4.174) and ( 31.000±4.659) ng/L re-spectively,P < 0.05 ]. Conclusion Intrathymus injection of allogenic antigen might induce specific im-mune tolerance to femur vein transplantation in rats.     

胸腺修饰诱导同种异体静脉移植的免疫耐受研究

Objective To investigate the possibility of inducing immune tolerance to vein trans-plantation in rats by intrathymic injection of allogene. Methods MHC antigen extracted from splenic cells of donor Wistar rats was intrathymically injected to recipients SD rats, and donor Wistar femur vein was transplanted after 2 weeks. Forty-eight SD rats were randomly divided into 4 groups: group A ( femur vein autograft) ,group B ( femur vein allograft) ,group C ( femur vein allograft with use of immunosuppressant), group D (intrathymus injection). Imaging, histology and immunological assays of these groups were carried out 2 weeks after the transplantation. Results Histologic parameters that were tested were better in group D than those in group B. The concentration of serum IFN-γ in group B was significantly higher than that in groups A, C and D [ ( 86. 707±10.928 ) ng/L vs (29.328±4. 170), (69.076±8.059) and (63.355± 4.895) ng/L respectively, P < 0.05 ]. The concentration of serum IL-4 in group B was obviously lower than in groups C and D [ (23.656±3.369) ng/L vs (29.425±4.174) and ( 31.000±4.659) ng/L re-spectively,P < 0.05 ]. Conclusion Intrathymus injection of allogenic antigen might induce specific im-mune tolerance to femur vein transplantation in rats.     

胸腺修饰诱导同种异体静脉移植的免疫耐受研究

Objective To investigate the possibility of inducing immune tolerance to vein trans-plantation in rats by intrathymic injection of allogene. Methods MHC antigen extracted from splenic cells of donor Wistar rats was intrathymically injected to recipients SD rats, and donor Wistar femur vein was transplanted after 2 weeks. Forty-eight SD rats were randomly divided into 4 groups: group A ( femur vein autograft) ,group B ( femur vein allograft) ,group C ( femur vein allograft with use of immunosuppressant), group D (intrathymus injection). Imaging, histology and immunological assays of these groups were carried out 2 weeks after the transplantation. Results Histologic parameters that were tested were better in group D than those in group B. The concentration of serum IFN-γ in group B was significantly higher than that in groups A, C and D [ ( 86. 707±10.928 ) ng/L vs (29.328±4. 170), (69.076±8.059) and (63.355± 4.895) ng/L respectively, P < 0.05 ]. The concentration of serum IL-4 in group B was obviously lower than in groups C and D [ (23.656±3.369) ng/L vs (29.425±4.174) and ( 31.000±4.659) ng/L re-spectively,P < 0.05 ]. Conclusion Intrathymus injection of allogenic antigen might induce specific im-mune tolerance to femur vein transplantation in rats.     

胸腺修饰诱导同种异体静脉移植的免疫耐受研究

Objective To investigate the possibility of inducing immune tolerance to vein trans-plantation in rats by intrathymic injection of allogene. Methods MHC antigen extracted from splenic cells of donor Wistar rats was intrathymically injected to recipients SD rats, and donor Wistar femur vein was transplanted after 2 weeks. Forty-eight SD rats were randomly divided into 4 groups: group A ( femur vein autograft) ,group B ( femur vein allograft) ,group C ( femur vein allograft with use of immunosuppressant), group D (intrathymus injection). Imaging, histology and immunological assays of these groups were carried out 2 weeks after the transplantation. Results Histologic parameters that were tested were better in group D than those in group B. The concentration of serum IFN-γ in group B was significantly higher than that in groups A, C and D [ ( 86. 707±10.928 ) ng/L vs (29.328±4. 170), (69.076±8.059) and (63.355± 4.895) ng/L respectively, P < 0.05 ]. The concentration of serum IL-4 in group B was obviously lower than in groups C and D [ (23.656±3.369) ng/L vs (29.425±4.174) and ( 31.000±4.659) ng/L re-spectively,P < 0.05 ]. Conclusion Intrathymus injection of allogenic antigen might induce specific im-mune tolerance to femur vein transplantation in rats.     

胸腺修饰诱导同种异体静脉移植的免疫耐受研究

Objective To investigate the possibility of inducing immune tolerance to vein trans-plantation in rats by intrathymic injection of allogene. Methods MHC antigen extracted from splenic cells of donor Wistar rats was intrathymically injected to recipients SD rats, and donor Wistar femur vein was transplanted after 2 weeks. Forty-eight SD rats were randomly divided into 4 groups: group A ( femur vein autograft) ,group B ( femur vein allograft) ,group C ( femur vein allograft with use of immunosuppressant), group D (intrathymus injection). Imaging, histology and immunological assays of these groups were carried out 2 weeks after the transplantation. Results Histologic parameters that were tested were better in group D than those in group B. The concentration of serum IFN-γ in group B was significantly higher than that in groups A, C and D [ ( 86. 707±10.928 ) ng/L vs (29.328±4. 170), (69.076±8.059) and (63.355± 4.895) ng/L respectively, P < 0.05 ]. The concentration of serum IL-4 in group B was obviously lower than in groups C and D [ (23.656±3.369) ng/L vs (29.425±4.174) and ( 31.000±4.659) ng/L re-spectively,P < 0.05 ]. Conclusion Intrathymus injection of allogenic antigen might induce specific im-mune tolerance to femur vein transplantation in rats.     

胸腺修饰诱导同种异体静脉移植的免疫耐受研究

Objective To investigate the possibility of inducing immune tolerance to vein trans-plantation in rats by intrathymic injection of allogene. Methods MHC antigen extracted from splenic cells of donor Wistar rats was intrathymically injected to recipients SD rats, and donor Wistar femur vein was transplanted after 2 weeks. Forty-eight SD rats were randomly divided into 4 groups: group A ( femur vein autograft) ,group B ( femur vein allograft) ,group C ( femur vein allograft with use of immunosuppressant), group D (intrathymus injection). Imaging, histology and immunological assays of these groups were carried out 2 weeks after the transplantation. Results Histologic parameters that were tested were better in group D than those in group B. The concentration of serum IFN-γ in group B was significantly higher than that in groups A, C and D [ ( 86. 707±10.928 ) ng/L vs (29.328±4. 170), (69.076±8.059) and (63.355± 4.895) ng/L respectively, P < 0.05 ]. The concentration of serum IL-4 in group B was obviously lower than in groups C and D [ (23.656±3.369) ng/L vs (29.425±4.174) and ( 31.000±4.659) ng/L re-spectively,P < 0.05 ]. Conclusion Intrathymus injection of allogenic antigen might induce specific im-mune tolerance to femur vein transplantation in rats.     

胸腺修饰诱导同种异体静脉移植的免疫耐受研究

Objective To investigate the possibility of inducing immune tolerance to vein trans-plantation in rats by intrathymic injection of allogene. Methods MHC antigen extracted from splenic cells of donor Wistar rats was intrathymically injected to recipients SD rats, and donor Wistar femur vein was transplanted after 2 weeks. Forty-eight SD rats were randomly divided into 4 groups: group A ( femur vein autograft) ,group B ( femur vein allograft) ,group C ( femur vein allograft with use of immunosuppressant), group D (intrathymus injection). Imaging, histology and immunological assays of these groups were carried out 2 weeks after the transplantation. Results Histologic parameters that were tested were better in group D than those in group B. The concentration of serum IFN-γ in group B was significantly higher than that in groups A, C and D [ ( 86. 707±10.928 ) ng/L vs (29.328±4. 170), (69.076±8.059) and (63.355± 4.895) ng/L respectively, P < 0.05 ]. The concentration of serum IL-4 in group B was obviously lower than in groups C and D [ (23.656±3.369) ng/L vs (29.425±4.174) and ( 31.000±4.659) ng/L re-spectively,P < 0.05 ]. Conclusion Intrathymus injection of allogenic antigen might induce specific im-mune tolerance to femur vein transplantation in rats.     

调节性T细胞在移植免疫耐受中的研究进展

诱导移植免疫耐受需产生免疫反应下调。多年来,被称为抑制性T细胞现被命名为调节性T细胞(regulatory T cells,Treg),Treg在免疫应答的负性调控中发挥着重要作用。Treg介导的连锁性抑制和传染性耐受解释了发挥免疫耐受的机制。Treg通过离体扩增后回输体内,有望成为移植免疫耐受新的免疫过继疗法。     

胸腺修饰诱导同种异体静脉移植的免疫耐受研究

Objective To investigate the possibility of inducing immune tolerance to vein trans-plantation in rats by intrathymic injection of allogene. Methods MHC antigen extracted from splenic cells of donor Wistar rats was intrathymically injected to recipients SD rats, and donor Wistar femur vein was transplanted after 2 weeks. Forty-eight SD rats were randomly divided into 4 groups: group A ( femur vein autograft) ,group B ( femur vein allograft) ,group C ( femur vein allograft with use of immunosuppressant), group D (intrathymus injection). Imaging, histology and immunological assays of these groups were carried out 2 weeks after the transplantation. Results Histologic parameters that were tested were better in group D than those in group B. The concentration of serum IFN-γ in group B was significantly higher than that in groups A, C and D [ ( 86. 707±10.928 ) ng/L vs (29.328±4. 170), (69.076±8.059) and (63.355± 4.895) ng/L respectively, P < 0.05 ]. The concentration of serum IL-4 in group B was obviously lower than in groups C and D [ (23.656±3.369) ng/L vs (29.425±4.174) and ( 31.000±4.659) ng/L re-spectively,P < 0.05 ]. Conclusion Intrathymus injection of allogenic antigen might induce specific im-mune tolerance to femur vein transplantation in rats.     

胸腺修饰诱导同种异体静脉移植的免疫耐受研究

Objective To investigate the possibility of inducing immune tolerance to vein trans-plantation in rats by intrathymic injection of allogene. Methods MHC antigen extracted from splenic cells of donor Wistar rats was intrathymically injected to recipients SD rats, and donor Wistar femur vein was transplanted after 2 weeks. Forty-eight SD rats were randomly divided into 4 groups: group A ( femur vein autograft) ,group B ( femur vein allograft) ,group C ( femur vein allograft with use of immunosuppressant), group D (intrathymus injection). Imaging, histology and immunological assays of these groups were carried out 2 weeks after the transplantation. Results Histologic parameters that were tested were better in group D than those in group B. The concentration of serum IFN-γ in group B was significantly higher than that in groups A, C and D [ ( 86. 707±10.928 ) ng/L vs (29.328±4. 170), (69.076±8.059) and (63.355± 4.895) ng/L respectively, P < 0.05 ]. The concentration of serum IL-4 in group B was obviously lower than in groups C and D [ (23.656±3.369) ng/L vs (29.425±4.174) and ( 31.000±4.659) ng/L re-spectively,P < 0.05 ]. Conclusion Intrathymus injection of allogenic antigen might induce specific im-mune tolerance to femur vein transplantation in rats.     

小鼠异体Sertoli细胞诱导胰岛移植免疫耐受的作用

Objective To study whether the sertoli cell allograft can achieve the immunotolerance and protect the co-transplant islet allograft on the heterotopic situation. Methods The diabetic C57 mice were used as recipients, and healthy BALB/C mice as islet donors,respectively. Healthy BALB/C and C57 mice were used as testis sertoli cell donors. The recipients were randomly divided into 4 groups,6 mice in each group : group A: only transplant with islet allograft;group B: co-transplant with islet allograft and serto-li isograft;group C:co-transplant with islet allograft and sertoli allograft;group D:sham-operated group. The blood and urine glucose levels in the models, and the survival time of the graft were observed. Results The mean survive time of graft in groups A, B, and C was (6.50±2.35 ), (55.67±4.84), and (51.33± 5.05 ) days respectively. In group D, blood glucose level was abnormal. The hyperglycemia of the diabetic C57 mice could be reversed by the transplant methods of groups B and C. The mean survival time in groups B and C was longer than in group A P < 0.05, but there was no significant differences between groups B and C,P > 0.05. Conclusion The sertoli cells can induce local immunotolerance and protect the co-transplant islet allograft. Sertoli cell isograft can obtain the same local immunotolerance as the sertoli cell allograft.     

小鼠异体Sertoli细胞诱导胰岛移植免疫耐受的作用

Objective To study whether the sertoli cell allograft can achieve the immunotolerance and protect the co-transplant islet allograft on the heterotopic situation. Methods The diabetic C57 mice were used as recipients, and healthy BALB/C mice as islet donors,respectively. Healthy BALB/C and C57 mice were used as testis sertoli cell donors. The recipients were randomly divided into 4 groups,6 mice in each group : group A: only transplant with islet allograft;group B: co-transplant with islet allograft and serto-li isograft;group C:co-transplant with islet allograft and sertoli allograft;group D:sham-operated group. The blood and urine glucose levels in the models, and the survival time of the graft were observed. Results The mean survive time of graft in groups A, B, and C was (6.50±2.35 ), (55.67±4.84), and (51.33± 5.05 ) days respectively. In group D, blood glucose level was abnormal. The hyperglycemia of the diabetic C57 mice could be reversed by the transplant methods of groups B and C. The mean survival time in groups B and C was longer than in group A P < 0.05, but there was no significant differences between groups B and C,P > 0.05. Conclusion The sertoli cells can induce local immunotolerance and protect the co-transplant islet allograft. Sertoli cell isograft can obtain the same local immunotolerance as the sertoli cell allograft.