ABSTRACT
<p><b>OBJECTIVE</b>To investigate the protective effects on allografts and the possible mechanism of adeno-associated heme-oxygenase-1 (AdHO-1) gene therapy against chronic rejection injury.</p><p><b>METHODS</b>Ex vivo AdHO-1 gene therapy was performed in vascular and renal transplantation models. The structure and function, the expression of therapeutic genes and proteins, and the immune modulation were analyzed.</p><p><b>RESULTS</b>AdHO-1 gene therapy protected renal transplant against chronic rejection, but the effect was not as remarkable as that in vascular transplant. The transfected empty vehicle aggravated chronic rejection damage in renal transplantation. AdHO-1 decreased the infiltration of macrophages and CD4(+) T cells.</p><p><b>CONCLUSIONS</b>AdHO-1 gene therapy can lessen damage of chronic rejection in allografts. It plays roles by protecting transplants, down-regulating immune response and inducing immune deviation.</p>
Subject(s)
Animals , Male , Rats , Adenoviridae , Genetics , Blood Vessels , Transplantation , CD4 Lymphocyte Count , Chronic Disease , Genetic Therapy , Methods , Genetic Vectors , Graft Rejection , Graft Survival , Heme Oxygenase-1 , Genetics , Kidney Transplantation , Methods , Macrophages , Pathology , Rats, Inbred Lew , Transfection , Transplantation, HomologousABSTRACT
OBJECTIVE@#To observe the effect of FTY720 and ICAM-1 mAb mono and combination therapy in mouse-to-rat cardiac xenotransplantation.@*METHODS@#Cardiac xenotransplantation was performed in abdominal site with micro-surgical technique. Recipients with xenografts were treated with different doses of FTY720 and/or ICAM-1 mAb. Graft survival, histopathology, infiltration of CD4+, and CD8+ T cells and levels of serum IL-2, IFN-gamma, IL-4, and IgM were investigated.@*RESULTS@#Survival time of xenografts was (2.75+/- 0.43)d in the controls, survival of grafts treated with ICAM-1 mAb did not significantly improve. Treatment with large dose FTY720 led to a survival of (4.25+/- 0.71)d (P<0.01). Combination therapy with large dose FTY720 and ICAM-1 mAb achieved a significant prolongation of graft survival with (10.25+/- 2.12)d (P<0.01). Levels of serum IL-2, IFN-gamma and rat-anti-mouse IgM decreased in the combined therapy group. Pathologic lesion and infiltration of T cells in xenografts showed mitigated in the large dose combined therapy group. There was a significant negative correlation between the antibody level and the graft survival time (R=-0.754, P<0.01).@*CONCLUSION@#The combined therapy of FTY720 and ICAM-1 mAb can achieve a significant effect in the prolongation of heart xenograft survival and inhibition of xenoantibodies.
Subject(s)
Animals , Female , Mice , Rats , Antibodies, Monoclonal , Therapeutic Uses , Dose-Response Relationship, Drug , Drug Therapy, Combination , Fingolimod Hydrochloride , Graft Rejection , Blood , Graft Survival , Heart Transplantation , Methods , Immunoglobulin M , Blood , Immunosuppressive Agents , Therapeutic Uses , Intercellular Adhesion Molecule-1 , Allergy and Immunology , Interferon-gamma , Blood , Interleukin-2 , Blood , Interleukin-4 , Blood , Mice, Inbred BALB C , Propylene Glycols , Therapeutic Uses , Rats, Wistar , Sphingosine , Therapeutic Uses , Time Factors , Transplantation, HeterologousABSTRACT
OBJECTIVE@#To explore the role of combined heart-thymus transplantation for heart allograft in rats.@*METHODS@#Vascularized heart-thymus combined transplantation was performed with microsurgical technique. Graft survival, histopathology, infiltration of CD4+, CD8+ T cells, level and mRNA expressions of IL-2 and IL-4 in the serum and cardiac grafts were investigated.@*RESULTS@#Heart allograft in the controls had a survival time of (6.0+/-0.76) d. heart-thymus combined transplantation in non-thymectomized rats had a survival time of (6.88+/-0.64)d (P<0.05). Heart-thymus combined transplantation in thymectomized rats led to an evident survival time of (14.13+/-5.82)d (P<0.01) for cardiac graft, which further obtained long term survival after short course of treatment with cyclosporine. Pathologic lesion and infiltration of CD4+ and CD8+ T cells in cardiac grafts showed mitigated in the long term survival group. IL-2 level in the serum and cardiac grafts maintained low level in the long term survival group, whereas IL-4 maintained high level.@*CONCLUSION@#Whether thymectomized or not in recipient rats, heart-thymus combined transplantation has a positive effect to protect cardiac graft. Furthermore, in thymectomized rats heart-thymus combined transplantation may lead to evident survival prolongation of the heart grafts, which induces immune tolerance in short course of treatment with cyclosporine.
Subject(s)
Animals , Male , Rats , CD4-Positive T-Lymphocytes , Allergy and Immunology , CD8-Positive T-Lymphocytes , Allergy and Immunology , Cyclosporine , Therapeutic Uses , Graft Survival , Allergy and Immunology , Heart Transplantation , Immune Tolerance , Allergy and Immunology , Immunosuppressive Agents , Therapeutic Uses , Interleukin-2 , Blood , Genetics , Interleukin-4 , Blood , Genetics , Rats, Sprague-Dawley , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction , Thymectomy , Thymus Gland , Transplantation , Time Factors , Transplantation Immunology , Allergy and Immunology , Transplantation, HomologousABSTRACT
OBJECTIVE@#To explore the role of allo heart and thymus transplantation by intrathymic inoculation of thymocytes.@*METHODS@#Wistar recipients were given intrathymic injection of allo thymocytes (2 x 10(7)) 14 days before the heart and/or thymus transplantation. Graft survival, histopathology, levels and mRNA expressions of IL-2, IL-4 in serum and cardiac-grafts were investigated.@*RESULTS@#Heart transplantation and heart-thymus composite transplantation with the treatment of CysA for 7 or 14 days prolonged graft survival. Heart transplantation and heart-thymus composite transplantation with intrathymic thymocytes injection induced the long-term survival of allo-grafts transiently immunosuppressed with CysA; IL-4 maintained at high levels but IL-2 kept at low levels in grafts in long-term survivals.@*CONCLUSION@#Intrathymic inoculation of allo thymoctyes can induce immune tolerance for both cardiac transplantation and heart-thymus combined transplantation in rats. Thymus graft may play a role in the induction and maintenance of central tolerance.
Subject(s)
Animals , Female , Rats , Cell Transplantation , Graft Rejection , Graft Survival , Heart Transplantation , Immune Tolerance , Interleukin-2 , Blood , Interleukin-4 , Blood , Rats, Sprague-Dawley , Rats, Wistar , Thymus Gland , Cell Biology , TransplantationABSTRACT
OBJECTIVE@#To observe the effect of cyclosporine and simulect mono or combination therapy on cardiac allo-transplantation in rats.@*METHODS@#Recipients with allografts were treated with different doses of cyclosporine and/or simulect after cardiac allo-transplantation. Graft survival time was observed; the histopathological examination of graft tissues was performed; and levels of serum IL-2 and IL-4 were determined.@*RESULTS@#Mono or combination therapy with cyclosporine and/or simulect increased the survival of cardiac allografts. With the prolongation of survival time of the grafts, the rejection of grafts was moderated. The serum IL-2 level increased in acute rejected grafts; the serum IL-4 level increased evidently in long survival grafts.@*CONCLUSION@#Cyclosporine and simulect have an effect in the prolongation of cardiac allograft survival in rats, and the combination therapy shows an evident synergistic effect.