ABSTRACT
The γc cytokines play an important role in proliferation and survival of T cells. Blocking the γc signals can cause the activated donor-reactive T cells losing the ability to proliferate, and getting into apoptosis pathway, which contributes to induction of the peripheral tolerance. In this study, we induced the transplant tolerance through blocking the γc in combination with donor-specific trans-fusion (DST) in the cardiac transplantation. Following DST, on the day 2, 4 and 6, C57BL/6 recipients received anti-γc monoclonal antibodies (mAbs) injection, and those in control group were not given anti-γc mAbs. On the day 7, Balb/c cardiac allografts were transplanted. All recipients in experimental group accepted cardiac allografis over 30 days, and two of them accepted allografis without rejection until sacrifice on the 120 day. Animals only receiving DST rejected gratis within 5 days, and the mice receiving cardiac transplantation alone rejected gratis within 9 days. Our study showed that blockade of γc signaling combined with DST significantly prolonged allografi survival, which was probably associated with inhibition of antigen-specific T-cell proliferation and induction of apoptosis.
ABSTRACT
Objective To acquire antigen specific CD8+CD28-Tr by donor specific transfusion (DST) in vivo, and evaluate their suppressive effect on the acute rejection responses in rat liver transplantation through adoptive transfer experiment. Methods DST was used to induce CD8 + CD28 Tr to LEW antigens in naive Brown Norway(BN) rat. Then the induced CD8+CD28- Tr were adoptively transferred into the recipients of LEW→BN liver transplantation, which were acute rejection models. The survival time and histological changes were observed. Statistic analysis was performed with Log-Rank test by SPSS11.0 software, to compare the survival rate. Results Adoptive transfer of the DST-induced CD8+CD28-Tr attenuated the acute rejection responses in acute rejection models of rat liver transplantation. Conclusion DST can induce large numbers of CD8+CD28-Tr in naive BN rats in vivo. The adoptive transfer of the induced CD8+CD28Tr suppressed the acute rejection responses in rat liver transplantation. DST may become one of the methods that induce antigen specific CD8+CD28- Tr in vivo.
ABSTRACT
The goal of the immunologic maneuvering for organ transplantation may be the donor specific immune tolerance rather than non-specific immunosuppression. Although DST is one of the most extensively studied methods for donor specific immune hyporesponsiveness, it is not widely used in recent years because of possible sensitization and overall improvement of graft survival without DST. Several human and animal studies showed that -24h DST with concomitant cyclosporine administration improved graft survival. -24 DST may not induce adverse sensitization that preclude subsequent transplantation and the procedure is simple and does not delay the operation in living donor transplantation. Between Feb. 1994 and Jan. 1997, 33 patients received 100-200ml of fresh whole blood from the kidney donor 1 day before transplantation. Twenty donors were living related and 13 donors were non- related. Mean age was 40(22-52). Two patients was diabetic. All but one received primary allograft. Cyclosporine and prednisolone were the primary immunosuppressants that started 2-3 days before transplantation. Acute rejection occurred in 11 recipients(33.3%). Acute rejection tended to occur earlier. Eight of 11 first episodes were within 3 days post- transplant, which were all recovered by either steroid pulse or OKT3. Mean follow up was 35 months. Two patients died with functioning graft. Three-year graft survival rate was 93.9%. There was no immunologic graft loss. We conclude that -24h DST may be a valuable option of immune modulation for renal transplantation with no demonstrable adverse reaction. It's beneficial effect needs to be confirmed by a larger controlled study.