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He Xu

Associate Professor of Surgery
Surgery, Surgical Sciences

Selected Publications


Rapamycin Prevents Expansion of Costimulation Blockade-resistant CD8+ Alloreactive Memory Cells following Depletional Induction in Renal Transplant Recipients.

Journal Article J 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 ... Full text Open Access Link to item Cite

Immunomodulation of T cell-mediated alloimmunity by proximity to endothelial cells under the mammalian target of rapamycin blockade.

Journal Article Am 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 ... Full text Link to item Cite

The Role of Autophagy in Vascular Endothelial Cell Health and Physiology.

Journal Article Cells · 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 ... Full text Link to item Cite

Xenorecognition and costimulation of porcine endothelium-derived extracellular vesicles in initiating human porcine-specific T cell immune responses.

Journal Article Am 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 ... Full text Open Access Link to item Cite

IFI16-STING-NF-κB signaling controls exogenous mitochondrion-induced endothelial activation.

Journal Article Am J Transplant · June 2022 Mitochondria released from injured cells activate endothelial cells (ECs), fostering inflammatory processes, including allograft rejection. The stimulator of interferon genes (STING) senses endogenous mitochondrial DNA, triggering innate immune activation ... Full text Open Access Link to item Cite

Modulation of Xenogeneic T-cell Proliferation by B7 and mTOR Blockade of T Cells and Porcine Endothelial Cells.

Journal Article Transplantation · 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 ... Full text Open Access Link to item Cite

Age-related effects on thymic output and homeostatic T cell expansion following depletional induction in renal transplant recipients.

Journal Article Am 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 ... Full text Open Access Link to item Cite

Kidney transplantation using alemtuzumab, belatacept, and sirolimus: Five-year follow-up.

Journal Article Am 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 ... Full text Link to item Cite

B cell reconstitution following alemtuzumab induction under a belatacept-based maintenance regimen.

Journal Article Am 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 ... Full text Link to item Cite

Circulating mitochondria in organ donors promote allograft rejection.

Journal Article Am 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. ... Full text Link to item Cite

IL-7 receptor heterogeneity as a mechanism for repertoire change during postdepletional homeostatic proliferation and its relation to costimulation blockade-resistant rejection.

Journal Article Am 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 ... Full text Link to item Cite

Place of Residence and Cognitive Function among the Adult Population in India.

Journal Article Neuroepidemiology · 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 ... Full text Link to item Cite

Thrombalexin: Use of a Cytotopic Anticoagulant to Reduce Thrombotic Microangiopathy in a Highly Sensitized Model of Kidney Transplantation.

Journal Article Am 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 ... Full text Link to item Cite

Postdepletion Lymphocyte Reconstitution During Belatacept and Rapamycin Treatment in Kidney Transplant Recipients.

Journal Article Am 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 ... Full text Link to item Cite

Renal transplantation using belatacept without maintenance steroids or calcineurin inhibitors.

Journal Article Am 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 ... Full text Link to item Cite

The allo- and viral-specific immunosuppressive effect of belatacept, but not tacrolimus, attenuates with progressive T cell maturation.

Journal Article Am 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 ... Full text Link to item Cite

Monocyte-derived CD40 expression is regulated by interferon-γ/interferon-γ receptor-1 pathway when acting as a bridge during their interaction with T cells and allogeneic endothelial cells.

Conference Transplant 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 ... Full text Link to item Cite

The interleukin-2 receptor α chain (CD25) plays an important role in regulating monocyte-derived CD40 expression during anti-porcine cellular responses.

Conference Transplant 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 ... Full text Link to item Cite

Tumor necrosis factor-α pathway plays a critical role in regulating interferon-γ induced protein-10 production in initial allogeneic human monocyte-endothelial cell interactions.

Conference Transplant 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 ... Full text Link to item Cite

Immunomodulation of human CD8⁺ T cells by thymoglobulin in vitro.

Conference Transplant 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 ... Full text Link to item Cite

Upregulation of molecules associated with T-regulatory function by thymoglobulin pretreatment of human CD4+ cells.

Journal Article Transplantation · 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 ... Full text Link to item Cite

Rabbit anti-human leukocyte polyclonal antibody inhibits xenogeneic cell-mediated immune responses.

Journal Article Transplant 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 ... Full text Link to item Cite

Reduced antigenicity of formaldehyde-fixed arterial allografts and their potential clinical application.

Journal Article Transplant 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 ... Full text Link to item Cite

Evaluation of CD86/CD28 and CD40/CD154 pathways in regulating monocyte-derived CD80 expression during their interaction with allogeneic endothelium.

Journal Article Transplant 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 ... Full text Link to item Cite

CD4+ T-cell and monocyte interdependence during discordant xenoimmune responses.

Journal Article Transplant 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 ... Full text Link to item Cite

A nuclear factor-kappaB inhibitor BAY11-7082 inhibits interactions between human endothelial cells, T cells, and monocytes.

Journal Article Transplant 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 ... Full text Link to item Cite

Conversion from mycophenolate mofetil to azathioprine in renal allograft [corrected] patients within the first month posttransplantation.

Journal Article Transplant 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 ... Full text Link to item Cite

Molecular characterization of hypoxia-hypothermia-conditioned human endothelial cells and their interaction with human monocytes.

Journal Article Transplant 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 ... Full text Link to item Cite

Dexamethasone suppresses DU145 cell proliferation and cell cycle through inhibition of the extracellular signal-regulated kinase 1/2 pathway and cyclin D1 expression.

Journal Article Asian 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 ... Full text Link to item Cite

Are we ready to utilize non-heart-beating donors for clinical allotransplantation in China?

Journal Article Transplant 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 ... Full text Link to item Cite

Clinical studies of hemodialysis access through formaldehyde-fixed arterial allografts.

Journal Article Kidney 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 ... Full text Link to item Cite

CD154 blockade, sirolimus, and donor-specific transfusion prevents renal allograft rejection in cynomolgus monkeys despite homeostatic T-cell activation.

Journal Article Transplantation · 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 ... Full text Link to item Cite

Platelet-derived or soluble CD154 induces vascularized allograft rejection independent of cell-bound CD154.

Journal Article J 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 ... Full text Link to item Cite

Human monocytes as intermediaries between allogeneic endothelial cells and allospecific T cells: a role for direct scavenger receptor-mediated endothelial membrane uptake in the initiation of alloimmunity.

Journal Article J 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 ... Full text Link to item Cite

Composite tissue allotransplantation: development of a preclinical model in nonhuman primates.

Journal Article Transplantation · 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, ... Full text Link to item Cite

IDEC-131 (anti-CD154), sirolimus and donor-specific transfusion facilitate operational tolerance in non-human primates.

Journal Article Am 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 ... Full text Link to item Cite

The clinical application of monoclonal antibody therapies in renal transplantation.

Journal Article Expert 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 ... Full text Link to item Cite

Effects of combined treatment with CD25- and CD154-specific monoclonal antibodies in non-human primate allotransplantation.

Journal Article Am 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 ... Full text Link to item Cite

Rabbit antithymocyte globulin induction and sirolimus monotherapy supports prolonged islet allograft function in a nonhuman primate islet transplantation model.

Journal Article Transplantation · 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 ... Full text Link to item Cite

Studies investigating pretransplant donor-specific blood transfusion, rapamycin, and the CD154-specific antibody IDEC-131 in a nonhuman primate model of skin allotransplantation.

Journal Article J 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 ... Full text Link to item Cite

Combination induction therapy with monoclonal antibodies specific for CD80, CD86, and CD154 in nonhuman primate renal transplantation.

Journal Article Transplantation · 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 ... Full text Link to item Cite

Humanized anti-CD154 antibody therapy for the treatment of allograft rejection in nonhuman primates.

Journal Article Transplantation · 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 ... Full text Link to item Cite

Pancreatic islet transplantation using the nonhuman primate (rhesus) model predicts that the portal vein is superior to the celiac artery as the islet infusion site.

Journal Article Diabetes · 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 ... Full text Link to item Cite

Efficacy and toxicity of a protocol using sirolimus, tacrolimus and daclizumab in a nonhuman primate renal allotransplant model.

Journal Article Am 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 ... Full text Link to item Cite

Human platelets activate porcine endothelial cells through a CD154-dependent pathway.

Journal Article Transplantation · 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 ... Full text Link to item Cite

Treatment with the humanized CD154-specific monoclonal antibody, hu5C8, prevents acute rejection of primary skin allografts in nonhuman primates.

Journal Article Transplantation · 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 ... Full text Link to item Cite

Induction therapy with monoclonal antibodies specific for CD80 and CD86 delays the onset of acute renal allograft rejection in non-human primates.

Journal Article Transplantation · 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 ... Full text Link to item Cite

Right ventricular outflow tract reconstruction using a Goretex membrane monocusp valve in infant animals.

Journal Article ASAIO 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 ... Full text Link to item Cite

A novel St. Jude medical prosthetic valve with silver coated sewing cuff in sheep mitral valve replacement

Journal Article Chest · 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 ... Cite

Prolonged discordant xenograft survival and delayed xenograft rejection in a pig-to-baboon orthotopic cardiac xenograft model.

Journal Article J 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 ... Full text Link to item Cite

Prolonged discordant cardiac xenograft survival in newborn recipients.

Journal Article Circulation · 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 ... Link to item Cite

Right ventricular outflow tract reconstruction using a Gore-Tex membrane monocusp valve in infant goats

Journal Article Chest · 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 ... Cite

In vitro evaluation of neonatal human immunity against the pig.

Journal Article J 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 ... Full text Link to item Cite

Newborn baboon immunity: lessons in cross-species transplantation.

Journal Article Ann 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 ... Full text Link to item Cite

Age-related development of human anti-pig xenoantibody.

Journal Article J 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 ... Full text Link to item Cite

Newborn baboon serum lacks natural anti-pig xenoantibody.

Journal Article Transplantation · 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 ... Link to item Cite

Absence of hyperacute rejection in pig-to-primate orthotopic pulmonary xenografts.

Journal Article Transplantation · 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 ... Link to item Cite

Absence of hyperacute rejection in newborn pig-to-baboon cardiac xenografts.

Journal Article Transplantation · 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 ... Full text Link to item Cite

Natural antipig xenoantibody is absent in neonatal human serum.

Journal Article J 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 ... Link to item Cite

Abrogation of baboon natural xenoantibody to pig splenocytes by DL-penicillamine.

Journal Article Transplantation · 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 ... Link to item Cite

Photochemotherapy in human heart transplant recipients at high risk for fatal rejection.

Journal Article J 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 ... Link to item Cite