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.     

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.     

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.     

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.     

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.     

门静脉输注供者脾细胞诱导的供者特异性免疫低反应性

目的 探讨经门静脉输注供者脾细胞能否诱导皮肤移植小鼠产生供者特异性的免疫低反应性及其可能机制.方法 取Balb/c小鼠,随机分为空白对照组(经小鼠门静脉输注RPMI 1640培养液)、受者脾细胞组(经小鼠门静脉输注Balb/c小鼠脾细胞)、供者脾细胞组(经小鼠门静脉输注C57BL/6小鼠脾细胞)、空白移植对照组(经小鼠门静脉输注RPMI 1640培养液,7 d后移植C57BL/6小鼠的皮肤)、实验对照组(经小鼠门静脉输注Balb/c小鼠脾细胞,7 d后移植C57BL/6小鼠的皮肤)、实验组(经小鼠门静脉输注C57BL/6小鼠脾细胞,7 d后移植C57BL/6小鼠的皮肤)以及第三方移植组(经小鼠门静脉输注C57BL/6小鼠脾细胞,7 d后移植C3H小鼠的皮肤).记录空白移植对照组、实验对照组、实验组和第三方移植组移植皮肤的存活时间,并观察移植皮肤的病理学变化;脾细胞输注后7 d,分别获取空白对照组、受者脾细胞组和供者脾细胞组小鼠的外周血、脾脏和肝脏,用流式细胞仪测定样本中CD4+CD25+Foxp3+调节性T淋巴细胞(CD4+CD25+Foxp3+Treg细胞)的比例.结果 实验组移植皮肤的存活时间为(19.8±4.6)d,明显长于空白移植对照组、实验对照组和第三方移植组,但仍未达到长期存活.皮肤移植后7 d,空白移植对照组和实验对照组的移植皮肤呈现重度急性排斥反应的病理学改变,而实验组移植皮肤呈现中度急性排斥反应的病理学改变.供者脾细胞组外周血、肝脏和脾脏中CD4+CD25+Foxp3+Treg细胞比例明显高于空白对照组和受者脾细胞组.结论 门静脉输注供者脾细胞可特异性地延长供者皮肤移植物的存活时间,减轻移植物的排斥反应,该效应可能与受者体内的CD4+CD25+Foxp3+Treg细胞增加有关.     

Ingested interferon-alpha prevents allograft islet transplant rejection

BACKGROUND: Ingested interferon (IFN)-alpha is a biological response modifier in experimental autoimmune encephalomyelitis and multiple sclerosis, and prevents type 1 diabetes in nonobese diabetic mice. Islet transplantation possesses significant potential advantages over whole-gland transplantation because it is simple, may achieve insulin independence, and has clear advantages over exogenous insulin therapy. Therefore, we examined whether ingested IFN-alpha, administered to islet allograft recipients, could prevent islet allograft rejection. METHODS: Recipient C3H mice (H2k) were made diabetic and either untreated or treated with 10-1000 international units (IU) of ingested murine IFN-alpha daily from day -7 through day +14 after transplantation for a total of 21 days. Seven days after diabetes induction, recipients received allograft islets isolated from C57BL.10 donors (H2b) under the kidney capsule and were followed for overt diabetes via elevated blood glucose. RESULTS: Control recipients and recipients fed 1000 IU all became diabetic by day 13, whereas mice ingesting IFN-alpha had delayed rejection for up to 27 (10 IU) to 29 days (100 IU) after islet transplantation. Treatment of recipients of islet allografts with ingested IFN-alpha doubles the time period before rejection compared with control mice. The feeding period with daily IFN-alpha was doubled from 21 days to 42 days in total, 7 days before transplantation and 35 days after transplantation. CONCLUSION: Treatment of recipients of islet allografts with prolonged ingested IFN-alpha prevents rejection in a subset of recipients. Ingested IFN-alpha may prevent rejection if given continuously after transplantation.     

Attenuation of Donor‐Reactive T Cells Allows Effective Control of Allograft Rejection Using Regulatory T Cell Therapy

Regulatory T cells (Tregs) are essential for the establishment and maintenance of immune tolerance, suggesting a potential therapeutic role for Tregs in transplantation. However, Treg administration alone is insufficient in inducing long‐term allograft survival in normal hosts, likely due to the high frequency of alloreactive T cells. We hypothesized that a targeted reduction of alloreactive T effector cells would allow a therapeutic window for Treg efficacy. Here we show that preconditioning recipient mice with donor‐specific transfusion followed by cyclophosphamide treatment deleted 70–80% donor‐reactive T cells, but failed to prolong islet allograft survival. However, infusion of either 5 × 10⁶ Tregs with direct donor reactivity or 25 × 10⁶ polyclonal Tregs led to indefinite survival of BALB/c islets in more than 70% of preconditioned C57BL/6 recipients. Notably, protection of C3H islets in autoimmune nonobese diabetic mice required islet autoantigen‐specific Tregs together with polyclonal Tregs. Treg therapy led to significant reduction of CD8⁺ T cells and concomitant increase in endogenous Tregs among graft‐infiltrating cells early after transplantation. Together, these results demonstrate that reduction of the donor‐reactive T cells will be an important component of Treg‐based therapies in transplantation.     

肝星状细胞对同种异体胰岛移植物的保护作用

目的 研究小鼠肝星状细胞对同种异体胰岛移植物的保护作用.方法 将糖尿病小鼠随机分为三组,分别为糖尿病组、单纯胰岛移植组及与肝星状细胞共同移植组.单纯移植组于肾被膜下移植入同种异体胰岛300个;共同移植组移植入肝星状细胞(3×105个)与同种异体胰岛(300个)混合物.分别于移植术后监测受体小鼠血糖值及正常血糖维持时间;血糖正常一周后移植组及糖尿病组小鼠分别采血检测血清中TGF-β,TNF-α,IL-1β,IFN-γ的含量,同时取出移植物进行免疫组织化学检测.结果 术后共同移植组受体正常血糖维持时间为(23.75±8.96)d,单纯胰岛移植组受体正常血糖维持时间为(11.9±6.92)d,差异有统计学意义(P<0.05);三组受体血清中TNF-α、IL-1β、IFN-γ含量差异无统计学意义(P>0.05),共同移植组受体血清中TGF-β含量为(2292.31±5.87)pg/ml,单纯移植组为(1246.55±38.91)pg/ml,两组比较差异有统计学意义(P<0.05);病理学结果显示共同移植组胰岛素表达量大,并且在移植物周围有生物包膜形成.结论 在同种异体移植模型中,肝星状细胞可能通过高分泌TGF-β、局部形成包囊等方式保护胰岛移植物并延长其存活时间.     

Transplant Islets Into the Pinna of the Ear: A Mouse Islet Transplant Model

BackgroundIslets transplanted under the ear skin would allow easy observation of the graft response and survival in vivo. This research was designed to establish an efficient mouse islet transplant model to probe the dynamic cellular interplay in vivo.MethodsGreen fluorescent protein transgenic mice and BALB/c mice were used as donors and recipients. All recipients were divided into 6 groups of 6 mice each. First, we treated the transplant recipients, including diabetes induction, autologous epididymal fat pad, and MATRIGEL transplant to the ears. Then, 1. we transplanted isolated islets to the ear/ear with fat/ear with MATRIGEL; and 2. transplanted islets with collagen + basic fibroblast growth factor or islets with collagen + vascular endothelial growth factor. Mice in the control group received a sham transplantation with phosphate buffer saline. All recipients were then observed for 30 days with blood glucose (BG) monitoring. Finally, ears were removed with graft on day 28 for histologic examination.ResultsIt was suggested that transplant of islets alone could not correct hyperglycemia. Fat, MATRIGEL, collagen, and growth factors have the similar function to form a microenvironment conducive to islet survival. The effect of islet transplantation for correcting hyperglycemia of the fat modification group was better than other groups (P < .05). BG could be normalized, and living islets were detected by anti-insulin immunohistochemistry.ConclusionsTransplant islets into the ear with transplanted autologous fat is the optimal way which can be used to analyze the allograft response in vivo and track cell population and migration using labels by confocal microscopy.     

抗原特异性CD4+CD25+T细胞对同种异体胰岛移植影响及作用机制研究

目的:探讨抗原特异性CD4+CD25+Treg细胞免疫对同种异体胰岛急性移植排斥反应的影响和机制。方法:用MACS分选供体抗原特异性CD4+CD25+Treg细胞免疫糖尿病BALB/cByJ受体小鼠，以ICR小鼠胰岛为供体行同种异体胰岛移植。观察移植后小鼠的存活时间、移植前后外周血CD4+和CD8+T细胞亚群的变化和移植物中Th1/Th2细胞因子mRNA表达水平的变化。结果:抗原特异性Treg细胞联合胰岛移植组(C组)胰岛移植物平均生存期为(34.57±17.15)d，显著长于单纯胰岛移植组(B组)的(10.6±1.82) d (P<0.01)；移植后第3天，C组外周血CD4+/CD8+的值显著低于B组(P<0.01)；C组移植物中IL-10,TGF-β mRNA表达比B组显著增强。B组移植物中IL-1β，IL-2及IFN-γ mRNA表达明显强于C组。结论:抗原特异性CD4+CD25+ Treg细胞可通过调节Th2/Th1之间的反应平衡而延长同种异体胰岛移植物的存活时间。     

Long-term islet graft survival in streptozotocin- and autoimmune-induced diabetes models by immunosuppressive and potential insulinotropic agent FTY720

BACKGROUND: Toxicity of current immunosuppressive agents to islet grafts is one of the major obstacles to clinical islet transplantation (Tx). This study was designed to assess the efficacy of FTY720, a novel immunomodulator with a unique mechanism of action, on islet graft survival and function in streptozotocin (STZ)- and autoimmune-induced diabetic recipients. METHODS: Islet allograft from BALB/C mice or islet isografts were transplanted into STZ-induced diabetic CBA mice and autoimmune nonobese diabetic (NOD) mice. FTY720 was administered orally at 0.5 mg/kg per day in STZ diabetic recipients or 3 mg/kg per day in NOD recipients after Tx. Functional status of the islet graft was monitored by measuring blood glucose daily. Insulin secretion from mouse islets was measured with an insulin scintillation proximity assay. RESULTS: Under the treatment of FTY720, long-term normoglycemia (>100 days) was achieved in 100% of STZ diabetic recipients and 50% of diabetic NOD recipients compared with a respective 11 and 7 days in untreated animals after allogeneic islet Tx. Normoglycemia persisted only temporarily (<4 weeks) in untreated NOD recipients of NOD islets, but was maintained for >100days with FTY720 treatment. Histologically, leukocyte infiltration observed in untreated animals was largely inhibited in FTY720-treated ones. Additionally, FTY720 stimulated insulin secretion from isolated islets by approximately twofold under both normoglycemic and hyperglycemic conditions. CONCLUSIONS: FTY720 is highly effective in protecting allo- and autoimmune response-mediated islet graft destruction without direct toxicity to the islets. The effect is likely attributable to its action in preventing effector lymphocyte infiltration into the grafted tissue.     

阻断ICOS/B7h信号的供体特异性输血对移植受体CD4+CD25+调节性T细胞的影响

目的 观察阻断ICOS/B7h信号的供体特异性输血(DST)对异基因小鼠心脏移植术后体内CD4+CD25+调节性T细胞(Treg)的影响.方法 按陈氏方法建立小鼠颈部异位心脏移植模型,实验分3组,异基因组及同基因组:供心分别来源于BALB/C和C57BL/6小鼠,受体均为C57BL/6小鼠,未予治疗.治疗组:移植当天给予受体鼠(C57BL/6)尾静脉注射5×106 ICOS-Fc靶定的供体(BALB/C)脾B淋巴细胞,d0～6连续给予受体鼠尾静脉注射ICOS-Fc 200 μg/d.术后统计各组移植物的存活时间,通过流式细胞术检测受体鼠外周血中CD4+CD25+Treg的亚群比例,利用逆转录-聚合酶链反应(RT-PCR)检测移植物中FOXP3的mRNA表达,在混合淋巴细胞反应中检测CD4+CD25+Treg对CD4+CD25-效应T细胞(Teff)的增殖抑制效率.结果 与异基因组比较,治疗组心脏移植物存活时间明显延长[(84.38±29.14)d比(7.00±0.76)d,P＜0.01].各组中,治疗组受体外周血中CD4+CD25+Treg亚群比例显著上调[(15.60±5.69)%,P＜0.01].与其他两组比较,治疗组心脏移植物中FOXP3 mRNA表达显著上调.以正常鼠为对照,耐受鼠脾脏中获取的CD4+CD25+Treg能够更高效地抑制CD4+CD25-Teff在混合淋巴细胞培养中的增殖效应.结论 通过阻断ICOS/B7h信号的DST可以诱导异基因小鼠心脏移植耐受,CD4+CD25+Treg在耐受的形成与维持中均起着重要作用.     

Fas配体表达对同种胰岛移植的影响

目的探究睾丸细胞FasL表达能否对共移植的胰岛移植物提供免疫豁免作用以及胰岛细胞FasL基因转染对同种胰岛移植的影响.方法将同种大鼠胰岛及睾丸细胞同时移植于糖尿病受体,重组腺病毒AdV-FasL感染胰岛细胞后移植,观察移植物存活情况、胰岛功能,并检测移植物内浸润淋巴细胞以及基因转染胰岛细胞凋亡情况.结果单纯移植胰岛组平均存活期为(6.3±0.56)?d.与胰岛细胞同时移植的睾丸细胞数增加至1×107时,存活期大于50?d(P＜0.05).表达FasL的睾丸细胞在移植物内诱导浸润淋巴细胞凋亡.FasL基因转染组出现排斥加速,存活期缩短至(3.4±0.24)?d.FasL转染的胰岛细胞在移植后24h见FasL表达,48h表达增强,移植后FasL转染胰岛细胞凋亡.结论表达FasL的睾丸细胞与胰岛同时移植可诱导活化的淋巴细胞凋亡,使胰岛移植物获得免疫豁免、存活期延长,但通过FasL基因转染使胰岛细胞直接表达FasL引起胰岛细胞凋亡和粒细胞浸润,导致排斥加速.     

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.