ABSTRACT
OBJECTIVE@#To evaluate the effect of anti-inducible costimulator monoclonal antibody (anti-ICOS-Ab) combined with low-dose cyclosporine (CsA) on the survival quality and chronic rejection of heart allografts in rats.@*METHODS@#The rats' heterotopic cardiac transplantation model was established by Ono's method. The recipient rats were randomly divided into an isotransplantation control group and an allotransplantation experiment group. The experiment group was re-classified into a placebo group, a normal-dose CsA group, an anti-ICOS-Ab group, a low-dose CsA group, and an anti-ICOS-Ab combined with low-dose CsA group. The survival time of grafts was monitored. The cardiac grafts were harvested for histological analysis. Flow cytometric analysis was employed to detect the population of CD25+CD4+ in peripheral lymphocytes from recipients with a long-term surviving graft.@*RESULTS@#The survival time of the cardiac allografts in CsA-treated groups was significantly longer than that in placebo group (P0.05). Compared with the normal-dose CsA group, the chronic rejection lesions of the anti-ICOS-Ab combined with low-dose CsA treatment group significantly were alleviated in the long-term survival grafts, and the proportion of CD4+CD25+ regulatory T cell increased in peripheral blood.@*CONCLUSION@#The anti-ICOS-Ab combined with low-dose CsA can prolong the survival of cardiac allografts and alleviate the chronic rejection significantly. The high expression level of CD4+CD25+ regulatory T cell is beneficial to the long-term survival of grafts.
Subject(s)
Animals , Rats , Antibodies, Monoclonal , Therapeutic Uses , Antigens, Differentiation, T-Lymphocyte , Allergy and Immunology , Chronic Disease , Cyclosporine , Therapeutic Uses , Drug Therapy, Combination , Graft Rejection , Drug Therapy , Graft Survival , Heart Transplantation , Inducible T-Cell Co-Stimulator Protein , Random Allocation , T-Lymphocytes, Regulatory , Allergy and ImmunologyABSTRACT
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.