ABSTRACT
The development of immunosuprressants has had a significant contribution to inhibition of acute allograft rejection. However, long-term graft survival has not been realized by immunosuppressants, probably because of their nonspecific suppression of T cell activity and nonimmune side effects. The ideal way to overcome the limitations of current immunosuppressants is to induce allograft-specific immune tolerance. Transplant immunologists are exerting their efforts in achieving transplantation tolerance using three different approaches; mixed hematopoietic chimerism, costimulatory blockade, and regulation by regulatory T cells. It is expected that transplantation tolerance will soon be established as a standard immunosuppressive regimen with little side effects in preventing and reversing allograft rejection.
Subject(s)
Allografts , Chimerism , Graft Survival , Immune Tolerance , Immunosuppressive Agents , T-Lymphocytes, Regulatory , Transplantation ToleranceABSTRACT
The development of immunosuprressants has had a significant influence on inhibition of acute allograft rejection. However, long-term graft survival has not been achieved by immunosuppressants, probably because of their nonspecific suppression of T cell activity and nonimmune side effects. The ideal way to overcome the limitations of current immunosuppressants is to induce allograft-specific immune tolerance. Transplant immunologists are exerting their efforts in achieving transplantation tolerance using four different approaches; costimulatory blockade, mixed hematopoietic chimerism, T cell depletion, and regulation by regulatory T cells. It is expected that transplantation tolerance will soon be established as a standard immunosuppressive regimen with little side effects in preventing and reversing allograft rejection.
Subject(s)
Allografts , Chimerism , Graft Survival , Immune Tolerance , Immunosuppressive Agents , T-Lymphocytes, Regulatory , Transplantation ToleranceABSTRACT
Organ transplantation is the optimal treatment for patients with an end-stage organ disease.The induction of donor-specific tolerance is necessitatd because of severe side-effects of immunosuppression and chronic rejection of the transplanted organ that defy management.Bone marrow infusion and costimulatory blockade are considered to be the most effective strategies to induce immune tolerance.This review briefly discusses the mechanism and clinical application of immune tolerance induced by bone marrow infusion combined with costimulatory blockade.
ABSTRACT
Objective:To study the influence of Costimulatory Blockade CTLA4Ig combined with rapamycin(RPM)on the survival of renal allografts in rats.Methods:BN→Lewis rat kidney transplantation was performed.The recipients were grouped into group1(control),group2(CTLA4Ig),group3(rapamycin,RPM) and group4(CTLA4Ig+RPM).The survival of renal allografts,serum creatinine of the recipients and the pathological changes of the allografts were observed.Results:Significantly prolonged allografts survival time was seen in group 2,3 and 4 compared with control,with the longest in group 4.The lowest serum creatinine and fewest lymphocytes infiltrating grafts were also seen in group4.Conclusion:Combined use of CTLA4Ig and rapamycin(RPM)may suppress renal allograft rejection effectively and promote further prolongation of the survival of renal allografts.