摘要:

Background.A balanced network of positive and negative T-cell co-stimulatory signals is important in regulating T-cell activation. Blocking CD28, CD154 (CD40L), or both co-stimulatory molecules has been efficacious in preventing acute allograft rejection in certain but not all transplantation models. In the present study, the authors tested the hypothesis that stimulating programmed death 1 (PD-1)–triggered negative signals concurrent with blocking CD154 co-stimulatory signals would facilitate islet allograft tolerance.Methods.The authors used a dimeric PD-L1 immunoglobulin (Ig) fusion protein to stimulate the inhibitory receptor PD-1, and a monoclonal antibody to block CD154. The effects of PD-1 engagement and CD154 blockade on lymphocyte activation were determined by cell proliferation, flow cytometry, and a model of islet transplantation.Results.PD-L1Ig inhibited the proliferation of both CD4+and CD8+T cells stimulated by anti-CD3. The inhibitory effect of PD-L1Ig was enhanced by concurrent blockade of CD154 co-stimulatory signals, as demonstrated by T-cell proliferation and expression of cell surface activation markers. PD-L1Ig and anti-CD154 also synergistically blocked the activation and maturation of antigen-presenting cells. In an islet transplantation model, treatment of recipient C57BL/6 (H-2b) mice with PD-L1Ig and anti-CD154 induced long-term survival of DBA/2 (H-2d) islet allografts, whereas treatment with each reagent alone failed to prevent islet allograft rejection.Conclusions.These results suggest that engaging the negative receptor PD-1 exhibits critical immunoregulatory effects in the allograft response, and blocking positive co-stimulatory molecules with active delivery of inhibitory signals may represent a novel therapeutic strategy in transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

This study evaluates the correlation of magnetic resonance angiography (MRA) and digital subtraction angiography (DSA) with the operative vessel findings in living kidney donors. The intraoperative vessel findings of 52 living renal donors were compared with the preoperative diagnoses of each imaging technique. Sixty-seven arteries were found during explantation. Forty kidneys showed a single arterial blood supply, and 12 kidneys showed a multiple arterial blood supply. No advantage of either imaging method was found for arterial imaging. There were 55 veins identified during organ harvesting. MRA could not determine the venous system in one donor (1.9%) and failed to detect one small pole vein in another. DSA did not yield a venous diagnosis in seven patients (13.5%) and yielded misdiagnoses in four patients. The correct diagnosis of renal donor veins differed significantly in favor of MRA (kappa 0.79 vs. 0.45;P=0.008). MRA is superior to DSA in assessing the renal vasculature in living kidney donors.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background.Donor-specific immune tolerance has been reported in isolated cases of kidney transplantation associated with bone marrow transplantation. The following is a description of a living donor liver transplantation for a hilar cholangiocarcinoma in a previous recipient of an allogeneic bone marrow transplant.Method.A right hemi-liver transplantation was performed using a liver allograft obtained from the same previous bone marrow donor. A neoadjuvant chemo-irradiation protocol was implemented before the procedure. Because of the presence of full chimerism, no immunosuppression has been necessary for the last 22 months.Results.Liver graft function has remained excellent, and a magnetic resonance imaging scan at one and a half years has shown no tumor recurrence. A control liver biopsy at 1 year showed no rejection.Conclusions.Neoadjuvant chemo-irradiation therapy and removal of all immunosuppression after liver transplantation formed the basic structure of this approach. Additional benefits provided by living donor liver transplantation included limitation of tumor progression by diminishing the pretransplantation waiting time, radical excision of the tumor through a complete hepatectomy, and optimal timing of the transplant procedure within a neoadjuvant chemo-irradiation protocol.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID