Anti-CD154 variably prolongs allograft survival in nonhuman primates. Rodent studies suggest that adding pretransplant donor-specific transfusion (DST) and/or rapamycin to anti-CD154 improves survival. The CD154-specific Ab IDEC-131 was tested alone and in combination with rapamycin for its ability to inhibit rhesus MLRs. The ability of the Ab to block endothelial activation was also assessed. ...

Organ transplantation is limited by the number of cadaveric human donor organs that become available. Xenotransplantation - the transplantation of organs and tissues between animal species - would supply an unlimited number of organs and offer many other advantages. The pig has been identified as the most suitable donor animal. Pig organs, when transplanted into humans or nonhuman primates, are...

NO derived from iNOS has been implicated in cardiac rejection. However, little is known about the role of the reactive nitrogen species, peroxynitrite. We examined the protective actions of a peroxynitrite decomposition catalyst WW85 in an experimental model of acute cardiac rejection. Heterotopic, abdominal transplantation of rat donor hearts was performed. Groups included: isografts, allograf...

T H E SEARCH for more effective and Jess broadly toxic immunosuppressive agents remains a major goal of transplantation research. One approach to achieving more specific immunosuppression is to target only those lymphocytes responding to an allograft by directing therapy at activation antigens. Of these antigens, the interleukin-2 receptor (IL-2R) has proven of particular interest, both because...

Treatment with a 2-week course of anti-CD154 antibody and a single transfusion of donor leukocytes (a donor-specific transfusion or DST) permits skin allografts to survive for >100 days in thymectomized mice. As clinical trials of this methodology in humans are contemplated, concern has been expressed that viral infection of graft recipients may disrupt tolerance to the allograft. We report tha...

Cytotoxic T lymphocyte antigen 4 (CTLA4) appears to negatively regulate T cell activation. One mechanism by which CTLA4 might antagonize T cell function is through inhibition of CD28 signaling by competing for their shared ligands B7-1 and B7-2. In addition, CTLA4 ligation could initiate a signaling cascade that inhibits T cell activation. To address whether CTLA4 could inhibit immune responses...

A rat model of orthotopic corneal graft rejection was used to investigate the effect of depletion of subpopulations of immune cells by treatment with monoclonal antibodies. Though CD4+ cells were not eliminated completely by anti-CD4 monoclonal antibodies there was a profound delay in the rejection times of orthotopic corneal allografts. Furthermore a third of the CD4+ depleted animals failed t...

Classic hyperacute rejection is dependent on the activation of terminal components complement. Recently, xenoantibodies with limited abilities to activate classical pathway complement in vitro have been implicated acute vascular xenografts. It unclear how these Abs affect their pathogenic activities vivo. In this study, we demonstrate ability an anti-Gal-α1,3Gal (Gal) IgG1, modest complement-ac...

Even though the etiology of chronic rejection (CR) is multifactorial, donor specific antibody (DSA) is considered to have a causal effect on CR development. Currently the antibody-mediated mechanisms during CR are poorly understood due to lack of proper animal models and tools. In a clinical setting, we previously demonstrated that induction therapy by lymphocyte depletion, using alemtuzumab (a...

PURPOSE OF REVIEW Developing tailored immunosuppression regimens requires sensitive, non-invasive tools for serial post-transplant surveillance as the current clinical standards with serum creatinine and proteinuria are ineffective at detecting subclinical rejection. The purpose of this review is: (i) to illustrate the rationale for allograft immune monitoring, (ii) to discuss key steps to brin...