Objective To introduce the research progress in the immune of composite tissue allotransplantation. Methods The related articles were reviewed to summarize the immune characteristics, experimental developments, and cl inical experiences of composite tissue allotransplantation. Results Composite allogeneic tissue is on the body surface, including the composition of the complex with high antigenicity. There are a lot of differences in the immune responsesbetween composite tissue allotransplantation and organ transplantation, such as immunosuppressant protocol, rejectiondiagnosis, and chronic rejection. Conclusion In the next study, it is urgently needed to learn these experiences and toestabl ish the special standard of composite tissue allotransplantation in induction of immune tolerance, local medication, and rejection diagnosis.
Abstract: Objective To study the antiacute rejection effect of Pachymic acid (PA) in heart transplantation rats, in order to select a new antirejection medicine with low side effect from traditional Chinese medicine. Methods We established the model by transplanting Wistar rats (32,donor) heart allografts into the abdomen of SD rats (32,receptor). The homologous hearttransplanted rats were then randomly divided into 4 groups with 16 rats in each group. Olive oil solution with PA 1 mg/(kg·d), PA 10 mg/(kg·d), Cyclosporine (CsA) 5 mg/(kg·d) and olive oil solution 0.5 ml/(kg·d) were respectively given intragastrically to lowdosage PA group, highdosage PA group, CsA group and the control group till the end of observation. Survival time of heart allografts, heart beating and the histological changes of allografts were examined and serum level of interleukin2 (IL-2) and interferon-γ (IFN-γ) were determined by enzymelinked immunosorbent assay (ELISA). Results Survival time in the highdosage PA group, the lowdosage PA group and the CsA group were 24.90±0.99 d, 15.50±1.60 d and 26.80±0.88 d respectively, which is much better than the control group (6.10±1.10 d, q=22.363, P=0.000; q=44.793, P=0.000; q=49.272,P=0.000). IL-2 serum level in the highdosage PA group, the lowdosage PA group and the CsA group were all lower than that in the control group (q=14.483, P=0.000; q=3.705, P=0.000; =21.418,P=0.000), whileIL-2 serum level in the highdosage group was lower than that in the lowdosage group (q=10.778,P=0.000). Similarly, IFN-γ serum level in the first three groups were all lower than that in the control group (q=16.508,P=0000; q=4.281, P=0.000;q=19.621, P=0.000) and IFNγ serum level in the highdosage group was also lower than that in the lowdosage group (q=14.975, P=0.000). Pathological examination 7 days after the surgery showed that pathologic lesion was much more relieved in the two PA groups and the CsA group than the control group. Conclusion Acute rejection of heart transplantation can be effectively suppressed by PA.
OBJECTIVE:To investigate the index of the rejection of lJle retinal pigment epithelium(RPE)cells transplantation.
METHOD:Allogenic RPE transplantation on rahbits by transcleral technique, the changes of interleukin-2 (IL-2) activity in peripheral blood and the effect of
immunoinhibitor (methylprednisonlone)were detected.
RESLILTS:In the group of simple transplantation,the IL-2 activity in peripheral blood begin to rise in the first day after operation. The peak value occured in the third day,and is still much higher than that of the control group in the 14th day,whereas in the group treated with immunoinhibitor ,there was no obvious difference in the first day after operatlon,in the third day,the IL-2 activity rises slightly,and returned to normal level in the 7th day.
CONCLUSION: After RPE transplantation, the level of IL-2 activity in peripheral blood might serve as an important index to determining and detecting the rejective response.
（Chin J Ocul Fundus Dis,1996,12: 239-241）
Objective To establish the rat orthotopic liver transplantation model by characterizing the blood supply of hepatic artery with the Cuff skill and the modified arterial sleeve anastomosis, to explore the possible mechanisms of acute rejection and the express of Fractalkine (Fkn) in the early stage after hepatic allograft operation. Methods SD rats were selected as donors and Wistar rats as receptor for the rejection model of orthotopic liver transplantation. Recipient rats were divided into 2 groups randomly after operationand the drugs were given intraperitoneally once a day in each group. In the experimental group, cyclosporine A (CsA) was delivered with 3 mg/kg. In the control group, only normal saline was given with 3 ml/kg. Condition of survivals were observed. The rejection actvity index (RAI) and the expression of Fkn of liver tissue were observed after 3rd, 5th and 7th days in 5 rats. The rest of rats in each group were fed and given drug or normal saline until they were died and the mean survival time were recorded. Results There were 18 survivals in control group, and 19 in experimental group after liver transplantation. Condition of survivals in experimental group was better than that of control group. The mean survival times of experimental group(19.50±4.51 days) was significantly longer than that of control group(7.60±1.60 days), showing statistically significant difference (P＜0.05). After 3rd, 5th and 7th days of transplantation, RAI of control group were 3.80±0.35,5.90±0.87 and 7.50±1.30,respectively;RAI of experimental group were 3.10±0.21,3.90±0.41 and 4.50±0.52.Therewasstatistically significant difference in RAI between 2 groups on the 7th day after transplantation (Plt;0.01). On the 3rd,5th and 7th days after transplantation, the Fkn of control group was 8.20±0.57,21.30±3.30 and 25.70±4.91, and that of experimental group was 8.30±0.56,10.30±0.67 and 11.70±1.23. There were statistically significant differences in Fkn between 2 groups on the 5th, 7th days after transplantation (Plt;0.01). Conclusion Fkn is a participant inacute rejection after the rat orthotopic liver transplantation and can be chosen as a useful target in the diagnosis of acute rejection. CsA has immunosuppressive property in the condition of acute rejection in the rat orthotopic liver transplantation, which may be result from the decreased the level of Fkn.
PURPOSE:To carry out preliminary study on immunogenicity or'the retina and provide theoretical bassis of transplant rejection of the retina.
METHODS:The allogeneic whole retinal or photoreceptor layer from C57BL/6 mice wer transplanted subcutaneously into BALB/C mice for antigen exposure and delayed hypersensitivity (DH) and modified 51Cr-release assay for specific cytotoxic T lymphoeytes (CTL)were emploied.
RESULTS:The allogeneic whole retinal transplantation gave rise to DH(Plt;0.05 )and increased function of CTL of which the killing rate was 33.4% in concentration of 1:90 comparing with negative group (4.8% in 1:90,Plt;0.05)and the risen function could be blocked by anti-CD8.
CONCLUSION:We deduce that allogeneic whole retina has immunogenicity and should pay attention to transplant rejection postoperatively.but the photoreceptor layer seems to have no immunogenicity and may be no transplant rejection after its transplantation.
（Chin J Ocul Fundus Dis,1997,13: 234-236）
Objective To study the effect of recombinant lentiviral vector mediated human hepatocyte growth factor (hHGF) gene-modified bone marrow mesenchymal stem cells (BMSCs) on the immunological rejection after allograft l iver transplantation in rats, and to reveal the mechanism of immune tolerance. Methods Eight male Sprague Dawley (SD)rats of clean grade (aged 3 to 4 weeks, weighing 75-85 g) were selected for the isolation and culture of BMSCs; 64 adult male SD rats of clean grade (weighing 200-250 g) were used as donors; and 64 adult male Wistar rats of clean grade (weighing 230-280 g) were used as receptors. After establ ishing a stable model of rat allogeneic l iver transplantation, 1 mL sal ine, 2 ×106/mL of BMSCs 1 mL, 2 × 106/mL of BMSCs/green fluorescent protein 1 mL, and 2 × 106/mL of BMSCs/hHGF 1 mL were injected via the portal vein in groups A, B, C, and D respectively. Then the survival time of the rats was observed. The hepatic function was determined and the histological observation of the l iver was performed. The hHGF mRNA expression was detected by RT-PCR, the level of cytokine including hHGF, interleukin 2 (IL-2), IL-4, IL-10, and interferon γ (IFN-γ) by ELISA assay, the level of apoptosis by TUNEL method, and the expression level of prol iferating cell nuclear antigen (PCNA) by immunohistochemical method. Results The survival time of group D was significantly higher than that of groups A, B, and C (P lt; 0.01); the survival time of groups B and C was significantly higher than that of group A (P lt; 0.01), but there was no significant difference between group B and group C (P gt; 0.05). RT-PCR demonstrated the transcription of hHGF mRNA in the grafts of group D; the serum cytokine hHGF reached to (6.2 ± 1.0) ng/mL. Compared with groups B and C, group D exhibited significant inhibitory effect, significantly improved l iver function, and showed mild acute rejection. In addition, the levels of cytokine IL-2 and IFN-γ decreased; the levels of cytokine IL-4 and IL-10 increased; the level of apoptosis reduced; and the expression level of PCNA increased. Except for the expression of IL-4 (P gt; 0.05), there were significant differences in the other indexes between group D and groups B, C (P lt; 0.05). Conclusion BMSCs/hHGF implanting to rat l iver allograft via portal vein can induce immune tolerance. Compared with injection of BMSCs alone, BMSCs/hHGF treatment can alleviate acute rejection and prolong the survival time significantly. The immunosuppressive effect of BMSCs/hHGF is correlated with Th2 shifts up of Th1/Th2 shift, reduced apoptosis, promoted l iver regeneration.
Limitation of donor source for allograft makes the research on xenograft progress. Pig is regarded as one of the ideal donor animals. The major obstacle in xenograft is hyperacute rejection, which is caused by complements after they are activated by xenogeneic antigens combined with natural antibodies. It has been confirmed that alpha-Gal is the major target antigen, whose expression is incharged by alpha-1,3 galactosyltransferase (alpha-GT). The approaches to overcome hyperacute rejection against alpha-Gal included: immunoadsorption of xenogeneic natural antibodies, lysis of antigen by enzyme and genetic manupilation to obtain animal lack of alpha-GT. Besides alpha-Gal, there were other antigens binding to human serum antibody, such as gp65 and gp100, which was expressed on PAEC after induced by TNF, the A-like antigen. But their function was still unknown. It was debatable on the role of MHC in xenograft. Both direct and indirect pathway were involved in cellular response in xenograft.
Insufficient supply of organ for allotransplantation made the study on finding new organ resources from animal progress. Pig is regarded as one of the optimal donor animals for human. The major obstacle in this field is hyperacute reaction (HAR), which is triggered after the xenogenic natural antibodies preexisting in recipient blood combine to the antigens on the surface of the endothelium and activate the complement system. alpha-Galactose residues (alpha-Gal) on the endothelial cell have been identified as the major xenoantigens. NJZ Pig has been closely breed since 1938, whose family history is clear. Tissue samples from heart, liver, kidney, pancreas, lung, small intestine, skin, spleen, thymus and lymph node were obtained and embedded in paraffin. The sections were performed the immunohistochemical staining with the sera from health volunteers (including all the blood types) as the primary antibodies as well as the biotin labeled bandeirae simplicifolia I isolectin B4 (BS I-B4), which has specific affinity to alpha-galactose. All the staining sections were compared with the tissues digested with alpha-galactosidase. There was no difference between the antigens recognized by sera of different blood types. alpha-Gal was still the major xenoantigen on the endothelial cells. There might exist non-alpha-Gal antigens on the distal convoluted tubules and collecting tubules of the kidney. There was no alpha-Gal distributing on the secreting part of pancreas, either the islet cells or the matrix cells, but surely on pancreatic duct and vessels. All the antigenity was destroyed after the enzyme digestion except that the small intestine gland still positive with the BS I-B4. alpha-Gal is the major xenogenic antigen in NJZ Pigs. There exist some unknown antigens on the distal convoluted tubules and collecting ducts of the kidney. The blood type of recipient is not the first affair to be considered in pig-to-human xenotransplantation. The specificity of BS I-B4 for the alpha-galactose needs more detail research.
A variety of benign and malignant disorders affecting the trachea can theoretically be treated by simple resection and subsequent end-to-end anastomosis of remained trachea. Unfortunately, it is feasible only when the affected tracheal length does not exceed 50% of the entire length in adults and about 30% in children. Tracheal transplantation may be a treatment option for those patients, but still has many problems to be solved, such as immunological rejection, revascularization, infection and granulation tissue hyperplasia. This review focuses on how to use different methods to inhibit immunological rejection of tracheal transplantation, and current research progress of immunological rejection in tracheal allograft.
OBJECTIVE: In the guinea pig-to-rat cardiac xenotransplantation model, the effect of complement depletion by using Chinese Cobra Venom Factor(CVF) on hyperacute rejection was evaluated. METHODS: Cardiac xenograft from guinea pig was transplanted into the abdomen of rat after the recipient being given i.p. a dose of CVF 0.20 microgram/g. the recipients were divided into group A (control group), group B (only given CVF), group C (CVF + Cytoxan + Splenectomy), group D (Cytoxan + Splenectomy) Cytoxan was injected into the abdominal cavity with a dose of 60 mg/Kg. The survival time of xenograft was measured and histologic observation was carried out after the cardiac arrest. RESULTS: The survival time of xenograft ranged from 15 to 3,120 minutes. There were significant difference among group A compared with group B and C (P lt; 0.01), and no difference between group A and group D, as well as group B and C (P gt; 0.05). There were significant difference between group B and D, as well as group C and D(P lt; 0.01). The histologic observation proved that the hyperacute rejection in group A and D was milder than group B and C. CONCLUSION: The study reveals that CVF can prolong the xenograft time by depleting complement activities and restricting hyperacute rejection in this model. Further basic and clinical study of effect of CVF in xenograft transplantation is worthwhile.
