Journal ArticleJ Immunol · November 1, 2024
Alemtuzumab induction with belatacept/rapamycin-based maintenance immunotherapy (ABR) prevents kidney allograft rejection and specifically limits early costimulation blockade-resistant rejection (CoBRR). To evaluate the mechanisms by which this regimen alt ...
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Journal ArticleAm J Transplant · October 18, 2024
Endothelial cells (ECs) are an initial barrier between vascularized organ allografts and the host immune system and are thus well positioned to initiate and influence alloimmune rejection. The mammalian target of rapamycin inhibitor rapamycin is known to i ...
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Journal ArticleCells · May 11, 2024
Autophagy is a highly conserved cellular recycling process which enables eukaryotes to maintain both cellular and overall homeostasis through the catabolic breakdown of intracellular components or the selective degradation of damaged organelles. In recent ...
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Journal ArticleAm J Transplant · July 2023
Porcine vascular endothelial cells (PECs) form a mechanistic centerpiece of xenograft rejection. Here, we determined that resting PECs release swine leukocyte antigen class I (SLA-I) but not swine leukocyte antigen class-II DR (SLA-DR) expressing extracell ...
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Journal ArticleTransplantation · May 1, 2022
BACKGROUND: Activation of porcine endothelial cells (PECs) is the mechanistic centerpiece of xenograft rejection. This study sought to characterize the immuno-phenotype of human T cells in response to PECs and to explore the immuno-modulation of B7 and mam ...
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Journal ArticleAm J Transplant · September 2021
Thymic output and homeostatic mature cell proliferation both influence T cell repopulation following depletional induction, though the relative contribution of each and their association with recipient age have not been well studied. We investigated the re ...
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Journal ArticleAm J Transplant · December 2020
Kidney transplant outcomes are limited by toxicities associated with calcineurin inhibitors and steroids. This trial was conducted to determine whether a costimulation blockade (CoB)-based regimen could achieve acceptable long-term outcomes and graft survi ...
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Journal ArticleAm J Transplant · March 2020
Lymphocyte depletion has been shown to control costimulation blockade-resistant rejection but, in some settings, to exacerbate antibody-mediated rejection (AMR). We have used alemtuzumab, which depletes T and B cells, combined with belatacept and rapamycin ...
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Journal ArticleAm J Transplant · July 2019
The innate immune system is a critical regulator of the adaptive immune responses that lead to allograft rejection. It is increasingly recognized that endogenous molecules released from tissue injury and cell death are potent activators of innate immunity. ...
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Journal ArticleAm J Transplant · March 2018
Kidney transplant patients treated with belatacept without depletional induction experience higher rates of acute rejection compared to patients treated with conventional immunosuppression. Costimulation blockade-resistant rejection (CoBRR) is associated w ...
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Journal ArticleNeuroepidemiology · 2018
BACKGROUND: The place of residence has been linked to cognitive function among adults in developed countries. This study examined how urban and rural residence was associated with cognitive function among adults in India. METHODS: The World Health Organiza ...
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Journal ArticleAm J Transplant · August 2017
Early activation of coagulation is an important factor in the initiation of innate immunity, as characterized by thrombotic microangiopathy (TMA). In transplantation, systemic anticoagulation is difficult due to bleeding. A novel "cytotopic" agent, thromba ...
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Journal ArticleAm J Transplant · February 2016
Belatacept is used to prevent allograft rejection but fails to do so in a sizable minority of patients due to inadequate control of costimulation-resistant T cells. In this study, we report control of costimulation-resistant rejection when belatacept was c ...
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Journal ArticleAm J Transplant · May 2014
Kidney transplantation remains limited by toxicities of calcineurin inhibitors (CNIs) and steroids. Belatacept is a less toxic CNI alternative, but existing regimens rely on steroids and have higher rejection rates. Experimentally, donor bone marrow and si ...
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Journal ArticleAm J Transplant · February 2014
Tacrolimus impairs allo- and viral-specific T cell responses. Belatacept, a costimulation-based alternative to tacrolimus, has emerged with a paradoxical picture of less complete control of alloimmunity with concomitant impaired viral immunity limited to v ...
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ConferenceTransplant Proc · May 2012
Previous studies have showed the lack of CD40 expression on monocytes during monocyte and endothelial cell (EC) interaction in the absence of T cells indicating that the interaction between T cells, monocytes, and ECs is required for monocyte-derived CD40 ...
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ConferenceTransplant Proc · May 2012
Long-term xenograft survival is limited by delayed xenograft rejection, and monocytes are thought to play an important role in this process. Although typically considered a T cell surface marker, interleukin 2 the receptor chain CD25 is also functional on ...
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ConferenceTransplant Proc · May 2012
T-cell infiltration of allografts is a major pathologic component defining acute rejection episodes (ARE). We have shown that monocytes interact with allogeneic endothelial cells (ECs) for costimulation to achieve T-cell allorecognition. However, the produ ...
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ConferenceTransplant Proc · May 2012
The major mechanism of thymoglobulin in inhibiting allograft rejection involves lymphocyte depletion. However, its role in modulating CD8(+) cells has remained unclear. This study evaluated the immunologic effects of thymoglobulin on human CD8(+) cells. Pu ...
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Journal ArticleTransplantation · November 27, 2008
BACKGROUND: This study evaluated the immunologic effects of thymoglobulin in modulating human CD4+ cells. METHODS: Human CD4+ cells were purified from peripheral blood mononuclear cells by negative selection method. CD4+ cells were pretreated with thymoglo ...
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Journal ArticleTransplant Proc · October 2008
We studied the interactions between human monocytes and porcine endothelial cells (PEC) as well as the effects of a new generation of rabbit anti-human leukocyte polyclonal antibody (newRALG) to inhibit xenogeneic cell-mediated immune responses. Human peri ...
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Journal ArticleTransplant Proc · October 2008
This study was performed to examine the antigenicity of formaldehyde-fixed arterial allografts and their potential clinical application for hemodialysis access. Human femoral arteries were fixed with formaldehyde. New Zealand white rabbits were immunized w ...
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Journal ArticleTransplant Proc · October 2008
This study was designed to examine the role of monocyte-derived CD80 in providing costimulation to CD4+ cells, and to determine whether monocyte-derived CD80 expression is regulated by CD86/CD28 and CD40/CD154 pathways during allogeneic immunoresponses. Hu ...
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Journal ArticleTransplant Proc · October 2008
This study was designed to examine our hypothesis that human monocytes provide missing constimulatory signals to host CD4+ cells during interactions with porcine endothelial cells (PECs). PECs were isolated from the aorta. Human CD4+ T cells and monocytes ...
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Journal ArticleTransplant Proc · October 2008
Costimulatory molecules play critical roles during cell-mediated immune responses. We undertook this study to determine whether CD154-CD40 interactions induced human endothelial cell (EC) activation via the nuclear factor (NF)-kappaB pathway, and whether t ...
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Journal ArticleTransplant Proc · September 2008
This retrospective study evaluated the safety of conversion from mycophenolate mofetil (MMF) to azathioprine (Aza) within the first month posttransplantation in 117 renal allograft patients concomittantly treated with cyclosporine (CsA) and prednisone. In ...
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Journal ArticleTransplant Proc · September 2008
This in vitro study was designed to characterize the molecular profiling of human endothelial cells (ECs) during the early phase of hypoxia-hypothermia (HH) conditioning and to evaluate their interactions with allogeneic monocytes. The HH-conditioned ECs w ...
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Journal ArticleAsian J Androl · July 2008
AIM: To determine the mechanisms of glucocorticoids in inhibiting advanced prostate cancer growth. METHODS: The cell proliferation and cell cycle of prostate cancer DU145 cells following dexamethasone treatment were determined by proliferation assay and fl ...
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Journal ArticleTransplant Proc · May 2008
The concept of brain death has not been accepted by the majority of Chinese. Importantly, it is not recognized as a legal entity. We have developed a non-heart-beating donation protocol based on literature searches (Medline, Ovid, and CNKI) and issues rela ...
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Journal ArticleKidney Int · November 2007
Efficient hemodialysis requires establishing a permanent stable vascular access. Our study was designed to evaluate formaldehyde-fixed arterial allografts as hemodialysis access for end-stage renal disease. Various parameters were determined for 68 formald ...
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Journal ArticleTransplantation · May 15, 2007
BACKGROUND: CD154-specific antibodies have been shown to prevent acute rejection in many preclinical models including nonhuman primates (NHPs). However, they have been ineffective in pilot clinical trials, suggesting a need for more robust preclinical anal ...
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Journal ArticleJ Clin Invest · March 2006
CD154 is a cell surface molecule expressed on activated T cells that binds to CD40, an activating molecule on APCs. Its blockade has been shown to prevent allograft rejection, presumably by interrupting interactions between T cells and APCs. It is known th ...
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Journal ArticleJ Immunol · January 15, 2006
Recipient monocytes, T cells, and donor endothelial cells (ECs) are recognized as critical components of allograft rejection. We have recently shown that human monocytes infiltrate vascularized allografts before clinical rejection and have thus hypothesize ...
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Journal ArticleTransplantation · November 27, 2005
BACKGROUND: Composite tissue allotransplantation (CTA) has been recently introduced as a potential treatment for tissue loss secondary to burns, injuries, or resections. However, the optimal strategies to prevent CTA rejection remain undefined. Presently, ...
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Journal ArticleAm J Transplant · May 2005
CD154-specific antibody therapy prevents allograft rejection in many experimental transplant models. However, initial clinical transplant trials with anti-CD154 have been disappointing suggesting the need for as of yet undetermined adjuvant therapy. In rod ...
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Journal ArticleExpert Opin Emerg Drugs · May 2004
Monoclonal antibodies have become valuable tools for the precise clinical manipulation of the immune system. These highly specific proteins have proven their usefulness in both the treatment and prevention of organ transplant rejection. Indeed, they are th ...
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Journal ArticleAm J Transplant · November 2003
The CD154-specific monoclonal antibody (Mab) hu5c8 greatly prolongs allograft survival in primates. The CD25-specific Mab daclizumab has not, to date, been paired with hu5c8. We evaluated the effects of hu5c8 in vitro, alone and in combination with daclizu ...
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Journal ArticleTransplantation · July 15, 2003
BACKGROUND: We reported that rabbit anti-thymocyte globulin (RATG) induction followed by maintenance immunosuppression with sirolimus supports human kidney allograft survival and asked if this combination would promote islet allograft survival in our prima ...
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Journal ArticleJ Immunol · March 1, 2003
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 ...
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Journal ArticleTransplantation · November 27, 2002
BACKGROUND: Antibodies and fusion proteins specific for CD80, CD86, and CD154 have shown promise as agents capable of inducing donor-specific tolerance in rodents. These agents have also been shown to be synergistic with one another in many settings of cou ...
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Journal ArticleTransplantation · October 15, 2002
The anti-CD154 antibody hu5C8 prevents acute allograft rejection and prolongs allograft survival after withdrawal of therapy in nonhuman primates. This study describes the use of hu5C8 as a rescue agent for rejection developing after the withdrawal of hu5C ...
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Journal ArticleDiabetes · July 2002
We've established a nonhuman primate islet allotransplant model to address questions such as whether transplanting islets into the gut's arterial system would more safely and as effectively support long-term islet allograft survival compared with the tradi ...
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Journal ArticleAm J Transplant · April 2002
A regimen combining sirolimus, tacrolimus, and daclizumab has recently been shown to provide adequate immunosuppression for allogeneic islet transplantation in humans, but remains unproven for primarily vascularized allografts. We evaluated this regimen fo ...
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Journal ArticleTransplantation · December 15, 2001
BACKGROUND: Delayed xenograft rejection is associated with endothelial cell activation, platelet sequestration, and subsequent thrombosis. We evaluated whether human platelets could directly activate porcine endothelium (PEC), and if so, whether this was m ...
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Journal ArticleTransplantation · November 15, 2001
BACKGROUND: Allogeneic skin transplantation remains a rigorous test of any immune intervention designed to prevent allograft rejection. To date, no single, clinically available immunosuppressant has been reported to induce long-term primary skin allograft ...
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Journal ArticleTransplantation · August 15, 2001
CD80 and CD86 (also known as B7-1 and B7-2, respectively) are both ligands for the T cell costimulatory receptors CD28 and CD152. Both CD80 and CD86 mediate T cell costimulation, and as such, have been studied for their role in promoting allograft rejectio ...
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Journal ArticleASAIO J · 2000
We examined the feasibility of using a polytetrafluoroethylene membrane (goretex) valve and transannular patch (TAP) for right ventricular outflow tract (RVOT) reconstruction in growing animal models. Eleven infant goats (Group A) and 12 infant sheep (Grou ...
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Journal ArticleChest · October 1, 1998
Purpose: Prosthetic valve endocarditis is one of the life-threatening complications after valve replacement, which develops presumably secondary to bacterial invasion to the fabric sewing ring. The antibacterial activity of silver-containing compounds has ...
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Journal ArticleJ Thorac Cardiovasc Surg · June 1998
OBJECTIVE: Our objectives were to study delayed xenograft rejection and the effectiveness of pretransplantation total lymphoid irradiation combined with immunosuppression on rejection in a pig-to-baboon cardiac xenograft model. METHODS: Baboons were treate ...
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Journal ArticleCirculation · November 4, 1997
BACKGROUND: We previously demonstrated very low levels of xenoreactive natural antibodies in newborns, suggesting the possibility of prolongation of xenograft survival in newborn recipients. We used a pig-to-newborn goat heterotopic cardiac xenograft model ...
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Journal ArticleChest · October 1, 1996
Purpose: Biological materials including homografts are used for right ventricular outflow tract (RVOT) reconstruction in infants, but frequently require late replacement because of intrinsic deterioration. We examined the feasibility of using a polytetrafl ...
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Journal ArticleJ Thorac Cardiovasc Surg · May 1996
The critical shortage of organ donors has greatly limited the number of clinical allotransplantations. This is particularly true for neonatal patients, for whom xenotransplantation could provide an alternative therapeutic option to allotransplantation. The ...
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Journal ArticleAnn Thorac Surg · December 1995
BACKGROUND: The critical shortage of organ donors has greatly limited the number of heart transplantations performed each year. This is particularly true of the newborn patient, for whom xenotransplantation may provide an alternative therapeutic option to ...
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Journal ArticleJ Thorac Cardiovasc Surg · October 1995
Human cytotoxic natural xenoantibodies are believed to be of the immunoglobulin M class in nature. However, a thorough understanding of the development of these natural antixenodonor xenoantibodies remains incomplete. In this study, serum samples were obta ...
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Journal ArticleTransplantation · April 27, 1995
Discordant xenotransplantation represents an attractive alternative to allotransplantation in light of the shortage of donor organs currently available for cardiac allotransplantation. Unfortunately, discordant xenotransplantation is still limited by hyper ...
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Journal ArticleTransplantation · February 15, 1995
The shortage of organ donors for transplantation is more pronounced for the lung than for any other solid organ. To address this problem, we evaluated the feasibility of pulmonary xenotransplantation. Preliminary investigations demonstrated that orthotopic ...
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Journal ArticleTransplantation · January 15, 1995
The shortage of organs for transplantation is especially severe for the critically ill newborn infant, for whom donors of the appropriate size are particularly scarce. One way to overcome this problem is to use animals in lieu of humans as organ donors. Th ...
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Journal ArticleJ Heart Lung Transplant · 1995
BACKGROUND: Discordant xenotransplantation represents an attractive alternative to allotransplantation in light of the current shortage of donor organs suitable for heart allotransplantation. Unfortunately, discordant xenotransplantation is still limited b ...
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Journal ArticleTransplantation · December 27, 1994
Natural xenoantibodies are believed to be IgM in nature and are known to play a critical role in the hyperacute rejection of distantly related xenografts. The purpose of this study was to determine whether the reducing agent DL-penicillamine could inactiva ...
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Journal ArticleJ Heart Lung Transplant · 1992
Heart transplant recipients in whom high levels of lymphocytotoxic antibodies directed towards a spectrum of histocompatibility antigens develop frequently represent difficult management problems. Recipients of multiple transplants and multiparous females ...
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