Abstract:
BACKGROUND:Blockade of costimulation signaling required for immune response, such as CD40/CD40L and CD28/B7, is a reasonable strategy to prevent rejection and in defined combinations may allow donor specific tolerance. Indeed, in rodents, costimulation blockade with CD28/B7 antagonists or with CD40Ig was able to induce regulatory T cells and transplant tolerance whereas in primates, anti-CD40 antibodies, anti-CD40L antibodies or CTLA4Ig, used as monotherapy, significantly delayed graft rejection. METHODS:Using an adeno-associated virus (AAV) vector mediated gene transfer of a human CD40Ig fusion protein (hCD40Ig) in primates, we evaluated the capacity of this costimulation blockade molecule interfering with CD40/CD40L signaling in prolonging kidney transplants in cynomolgus monkeys. RESULTS:This gene transfer strategy allowed for maintaining a plateau of hCD40Ig production within two months and avoided a high-scale production phase of this molecule. Although the hCD40Ig was able to bind efficiently to human and macaque CD40L and high (>200 μg/ml) transgene expression was obtained, no effect on graft survival was observed. In addition, there was no inhibition of humoral response to vaccination. In vitro, hCD40Ig strongly increased mixed lymphocyte reaction, and when compared to the anti-CD40L antibody h5C8, was not as potent to induce complement-dependent cytotoxicity. CONCLUSION:These data suggest that CD40/CD40L blockade using a non-depleting CD40Ig fusion protein, a therapeutic strategy that showed efficacy in rodents, is not able to modulate the immune response in primates. These data highlight important biological differences between rodent and primate models to evaluate therapeutic strategies at the preclinical level.
journal_name
Transpl Immunoljournal_title
Transplant immunologyauthors
Angin M,Poirier N,Dilek N,Le Guiner C,Toromanoff A,Blancher A,Cherel Y,Deschamps JY,Tillou X,Renaudin K,Minault D,Hervouet J,Blancho G,Vanhove B,Anegon I,Le Mauff Bdoi
10.1016/j.trim.2012.10.004subject
Has Abstractpub_date
2012-12-01 00:00:00pages
139-45issue
4eissn
0966-3274issn
1878-5492pii
S0966-3274(12)00098-6journal_volume
27pub_type
杂志文章abstract:BACKGROUND:The importance of apoptosis contra necrosis for ischemia/reperfusion (RP) and acute rejection in concordant rodent xenotransplantation is largely unknown. We explored this question by comparing rodent allo and concordant xenotransplants with different morphological methods to detect apoptosis and biochemical...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/S0966-3274(03)00018-2
更新日期:2003-10-01 00:00:00
abstract::Limiting dilution analysis technique was used to enumerate the circulating precursor frequency of donor and third-party-reactive helper T lymphocytes (HTLpf) in 28 renal allograft recipients before (pre-tx) and at three intervals (T1: 60-90 days, T2: 120-180 days, T3: 360-1620 days) after transplantation (post-tx). Tw...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(97)80048-2
更新日期:1997-06-01 00:00:00
abstract:BACKGROUND:Response to Hepatitis B virus (HBV) vaccination can be diminished in some (50-80%) but not all dialysis patients. We hypothesized, that the response to vaccination on dialysis may correlate with the development of anti-HLA antibodies after renal transplantation and might therefore be a valuable parameter to ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2017.04.003
更新日期:2017-06-01 00:00:00
abstract::RNA interference (RNAi) has recently emerged as an efficient method to silence gene expression in mammalian cells by transfection of small interfering RNAs (siRNAs). The Janus kinase 3 (JAK3) is also pertinent to the development of a new immuno-suppressant. This study aimed to inhibit JAK3 expression using RNAi to det...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2009.02.004
更新日期:2009-05-01 00:00:00
abstract:BACKGROUND:After lung transplantation, the major complication limiting the long-term survival of allografts is obliterative bronchiolitis (OB), characterized by chronic rejection. Innate immune responses contribute to the development of OB. In this study, we used a murine heterotopic tracheal transplantation mouse mode...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2018.11.006
更新日期:2019-04-01 00:00:00
abstract::Transplant rejection is a multifactorial process involving complex interactions between components of the innate and the acquired immune system. In view of the shortage of donor organs available for transplantation, xenotransplantation of pig organs into man has been considered as a potential solution. However, in com...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/s0966-3274(02)00042-4
更新日期:2002-05-01 00:00:00
abstract:OBJECTIVE:To investigate the expression and significance of Sirt1 in renal allografts at the early stage of chronic renal allograft dysfunction (CRAD). METHODS:CRAD rat models were established using classical orthotopic F344-Lewis kidney transplantation. F344 and Lewis uninephrectomized rats were used as controls. Twe...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2018.02.006
更新日期:2018-06-01 00:00:00
abstract:BACKGROUND:Correct identification of the specificity of antibodies directed against HLA using single antigen Luminex beads (SALB) is essential in current HLA laboratory practice for transplantation. The aim of this study was to investigate the magnitude of concordance and discordance among laboratories in testing for a...
journal_title:Transplant immunology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.trim.2014.10.003
更新日期:2015-01-01 00:00:00
abstract::Today, most clinically used methods for analysis of alloreactivity in organ transplantation are based on humoral immunity. In order to study the cellular alloresponse, a rat kidney transplantation model with culturing of graft infiltrating lymphocytes was developed. Kidney transplantations between inbred rat strains w...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(99)80001-x
更新日期:1999-12-01 00:00:00
abstract::Chronic allograft dysfunction is one of the most important reasons for late graft loss after renal transplantation. Its etiology is multifactorial and combines immunological as well as non-immunological mechanisms. It is known from large registry data that MHC mismatches are inversely correlated to long term allograft...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2009.09.007
更新日期:2010-02-01 00:00:00
abstract:BACKGROUND:Mesenchymal stem cells (MSCs) can be used for immunomodulation therapy after solid organ transplantation. Here, we focus on the immunoregulatory potential of combination therapies of MSCs and classic pharmacotherapy to mediate acceptance of solid organ grafts. METHODS:To determine which drugs influence the ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2011.06.002
更新日期:2011-09-01 00:00:00
abstract::Since data on human herpesvirus 8 (HHV-8) infection in Spain is not available, our purpose was to determine the prevalence of HHV-8 infection and the risk of developing Kaposi's sarcoma (KS) among organ transplant recipients in different geographical areas of Spain. The study population consisted of 1019 liver and kid...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2006.09.008
更新日期:2006-12-01 00:00:00
abstract::Desferrioxamine (DFO), commonly used in therapy as a chelator of ferric ion in disorders of iron overload, is a potent inhibitor of human cytomegalovirus (HCMV) replication in cultured fibroblast cells. Moreover, DFO has immunomodulatory activity both in vitro and in vivo. We studied DFO effects on HCMV replication in...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/0966-3274(95)80017-4
更新日期:1995-12-01 00:00:00
abstract::Rituximab is frequently used in the setting of ABO-incompatible renal transplants, and highly sensitized patients. Its interference with B-cell flow cytometric crossmatch (B-FCXM) is well known. However, its effect on the T-cell flow cytometric crossmatch (T-FCXM) has not been described. We aimed to evaluate the effec...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2020.101360
更新日期:2021-02-01 00:00:00
abstract::Recently, the signal transducer and activator of transcription 4 (STAT4) gene have been associated with multiple autoimmune diseases. Taking into consideration that the different autoimmune diseases may share some common pathogenetic pathways, the aim of the present study was to evaluate the role of STAT4 rs7574865 po...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2011.01.001
更新日期:2011-05-01 00:00:00
abstract::Administration of anti-D immunoglobulin to D- women after delivery of a D+ infant has dramatically reduced the number of immunised women and cases of haemolytic disease of the fetus and newborn. The use of monoclonal anti-D might alleviate some of the pressures on maintaining adequate supplies of plasma sourced anti-D...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/s0966-3274(02)00066-7
更新日期:2002-08-01 00:00:00
abstract:BACKGROUND:Graft-versus-host disease is one of the major complications after allogeneic bone marrow transplantation, but it is not easy to anticipate the onset. Cytokines released by type 1 T helper cells are thought to play a pivotal role in acute graft-versus-host disease aGVHD. The ability to predict the likely occu...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2005.10.002
更新日期:2006-01-01 00:00:00
abstract::Treatment with autologous bone marrow transplantation (ABMT) can change the natural history of diabetes in patients with new-onset Type 1 diabetes (T1D). Effects of syngeneic bone marrow transplantation (syn-BMT) on diabetic nephropathy were studied in streptozotocin-induced diabetic mice. Diabetic mice received sibli...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2009.12.003
更新日期:2010-02-01 00:00:00
abstract::The expression of CD30 is restricted to cells of the immune system and strictly regulated under physiological conditions. However, active immune cells express CD30 and soluble CD30 (sCD30) is released. Several investigators reported the relevance for sCD30 as a predictive marker for allograft rejection following organ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2010.07.001
更新日期:2010-08-01 00:00:00
abstract:OBJECTIVES:To assess the timelines of serum free light chain (sFLC) concentrations and the kappa/lambda light chain (K/L) ratio in heart transplant (HTX) recipients. To analyze the performance of serum protein electrophoresis (SPE), serum immunofixation (sIFE) and sFLC measurements for gammopathy detection following a ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2017.01.003
更新日期:2017-03-01 00:00:00
abstract::National registry data indicate a trend towards the incorporation of lymphocyte depletion antibody induction therapy into immunosuppressive regimens for solid organ transplantation. Depletional induction has been shown to reduce the risk of early acute rejection, but increase the risk of immune incompetence. As such, ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2008.09.003
更新日期:2008-11-01 00:00:00
abstract:BACKGROUND:Every transplanted organ relies on a reliable and sound vascular system. Therefore, our study focused on the investigation if platelet inhibition alone or combined with mTOR-inhibition has a beneficial effect on the microvascular integrity in allogeneic murine skin grafts. METHODS:Skin transplantation was p...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2015.09.005
更新日期:2015-11-01 00:00:00
abstract::Administration of anti-intercellular adhesion molecule (ICAM)-1 monoclonal antibody (mAb) plus anti-lymphocyte function associated antigen (LFA)-1 mAb induces tolerance in murine cardiac transplantation, while anti-vascular cell adhesion molecule (VCAM)-1 mAb plus anti-very late antigen (VLA)-4 mAb administration prol...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(99)80021-5
更新日期:1999-03-01 00:00:00
abstract::Keratinocytes are activated to express MHC class II and ICAM-1 molecules during cutaneous inflammatory reactions. It is controversial how the interaction between these 'nonprofessional' antigen presenting cells (APC) and infiltrating T cells affects the local inflammatory response. To address this issue we analyzed wh...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/0966-3274(93)90059-h
更新日期:1993-01-01 00:00:00
abstract::C3H mice were immunized by repeated skin grafting with B10.BR tail skin. Ten days after the last immunization mice received 100 micrograms (intravenously) of a variety of different monoclonal antibodies (mAbs: anti-ICAM-1, -LFA-1, -VCAM-1, -VLA-4), alone or in combination, followed by further B10.BR skin grafts. Contr...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/0966-3274(95)80007-7
更新日期:1995-03-01 00:00:00
abstract::The outcome of hyperacute grade 3-4 steroid-refractory graft-versus-host-disease (SR-GVHD) remains dismal despite a plethora of agents being tried alone or in combination. Following T replete haploidentical transplantation with post-transplantation cyclophosphamide on 75 patients, 10 patients (13%) aged 2-20years, dev...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2016.08.009
更新日期:2016-11-01 00:00:00
abstract::Despite improvements in the prevention and treatment of graft-versus-host disease (GvHD) this allogeneic immune response is still one of major complications following allogeneic stem cell transplantation (SCT). Identification of patients at risk for the development of acute and chronic GvHD would facilitate early inte...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2012.07.003
更新日期:2012-12-01 00:00:00
abstract::4-1BB, a member of the tumor necrosis factor (TNF) receptor superfamily, interacts with 4-1BBL expressed on APC and delivers a costimulatory signal for T cell activation and growth. In this study, we investigated the efficacy of an adenoviral vector encoding murine 4-1BB extracellular domain and human IgG1 Fc (Ad4-1BB...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2006.03.010
更新日期:2006-08-01 00:00:00
abstract:BACKGROUND:Donor specific hematopoietic cell transplantation has long been recognized for its potential in tolerance induction for subsequently transplanted organs. We have recently published that co-administration of Myeloid Progenitor (MP) and third party Hematopoietic Stem Cells (HSC) can induce MP-specific toleranc...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2014.04.001
更新日期:2014-08-01 00:00:00
abstract::Graft rejection and graft-versus-host disease are leading causes of transplant related mortality despite advancements in immunosuppressive therapy. Mesenchymal stem cells (MSCs) offer a promising addition to immunosuppressive drugs (ISD), while NK-cells are increasingly used as effector cells in graft-versus-leukemia....
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2016.04.008
更新日期:2016-07-01 00:00:00