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 data on the levels of high-energy phosphates obtained with in vitro 31Phosphorous Magnetic Resonance Spectroscopy (31P MRS). More specifically, we applied a hitherto unused method in transplantation research, apoptosis specific biotin labeled oligonucleotides designed with a 10 base pair stem region and a 20 nucleotides large loop that form a hairpin like shape. The results obtained with this method were compared to results obtained with the more widely used in situ 3'-end labeling of DNA (TUNEL) assay and extraction and gel electrophoresis of labeled DNA (DNA laddering). METHODS:Cervical heart transplantations were performed between inbred Lewis (L) (RT1l) to L, L to DA (RT1a) rats, hamster (H) to H and H to L (X) (n=5 for all groups except for X, n=9). All hearts were subjected to 30 min of cold ischemia (+4 degrees C) and 6 h of RP before explantation. In vitro 31P MRS was used to determine the phosphocreatine (PCr), beta-adenosine triphosphate (beta-ATP) concentrations and the PCr/beta-ATP ratio of the transplants. We correlated the biochemical data to haematoxylin and eosin (H & E) stained tissue slides scored for rejection, infiltration of antibodies and complement depositions, DNA extraction and gel electrophoresis of labeled DNA (DNA laddering), in situ 3'-end labeling of DNA (TUNEL) and the apoptosis specific hairpin probe assays scoring. RESULTS:The rejection score of the xeno grafts differed significantly compared to their syngeneic hamster to hamster controls (2.40 +/- 0.25 vs. 1.20 +/- 0.20; P=0.005) and they had a significantly higher TUNEL score, 228 +/- 15 vs. 2.44 +/- 0.32 (P=0.009), that correlated to changes in PCr concentration (P<0.001) and to the PCr/beta-ATP ratio (P=0.01). The uptake was mainly (90-95%) located to 1-2 microm large extra cellular 'granule'. A picture resembling early necrosis was seen on the H & E stainings and reflected in the Billingham rejection score above. CONCLUSIONS:After 6 h of RP the onset of acute rejection in the concordant hamster xeno hearts displayed features of early, possibly mitochondrial, necrosis, but not apoptosis, which correlated to changes in the PCr concentration and the PCr/beta-ATP ratio. The mechanism for the early rejection observed is unclear and might be caused by other factors in the sera apart from cellular components, antibodies and complement factors. Identification of the underlying mechanisms could enable us to design rational therapies that prevent activation of the recipient's innate immune response.
journal_name
Transpl Immunoljournal_title
Transplant immunologyauthors
Lukes DJ,Tivesten A,Wilton J,Lundgren A,Rakotonirainy O,Kjellström C,Isgaard J,Karlsson-Parra A,Soussi B,Olausson Mdoi
10.1016/S0966-3274(03)00018-2subject
Has Abstractpub_date
2003-10-01 00:00:00pages
29-40issue
1eissn
0966-3274issn
1878-5492pii
S0966-3274(03)00018-2journal_volume
12pub_type
杂志文章abstract::Induction of donor-specific hyporesponsiveness would minimize the need for intensive immunosuppression in the clinical setting of graft rejection and dendritic cells (DCs) might be useful tools for this purpose. Besides their ability to induce immunogenic T-cell responses, these antigen presenting cells can lead to T-...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2006.03.001
更新日期:2006-06-01 00:00:00
abstract::Over the last 25 years the importance of the humoral presensitization status of transplant recipients has increasingly been recognized. With greater understanding of the precise specificity of the pretransplant antibody status of recipients it is clear that the graft survival figures will improve. The development of n...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/0966-3274(94)90045-0
更新日期:1994-06-01 00:00:00
abstract:BACKGROUND:Cytomegalovirus (CMV)-specific T-cells are crucial to prevent CMV disease. CMV seropositive recipients transplanted with stem cells from a CMV seronegative allogeneic donor (R+D-) may be at risk for CMV disease due to absence of donor CMV-specific memory T-cells in the graft. METHODS:We analyzed the duratio...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2018.04.003
更新日期:2018-08-01 00:00:00
abstract::The imbalance of Th1/Th2 cytokines is well known in recurrent spontaneous abortion (RSA) mouse model. Mesenchymal stem cells (MSCs) possess potent immunoregulatory properties that could modulate the Th1 cytokine responses in benefit of Th2 types. In this study, we aimed to analyze the local and systemic balance of Th1...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2018.01.002
更新日期:2018-04-01 00:00:00
abstract:BACKGROUND:Endothelial microparticles (EMPs) are membrane vesicles shed from endothelial cell in response to injury, activation or apoptosis. Kidney transplantation (KTx) is the treatment of choice for patients with end stage kidney disease (ESKD). The aim of this study was to analyze changes in EMP and serum creatinin...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2014.06.006
更新日期:2014-08-01 00:00:00
abstract::Mouse hearts transplanted into MHC disparate donors are usually rejected 1 week after placement. It is widely accepted that alloantigen-reactive helper T lymphocytes (HTL) and cytotoxic T lymphocytes (CTL) are the key mediators of acute allograft rejection. This report demonstrates that the presence or absence of 'tra...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/0966-3274(95)80028-x
更新日期:1995-09-01 00:00:00
abstract:AIM:To investigate the influence of immunosuppressants on the fertility of males who undergo renal transplantation as well as on the immune function of their offspring. METHODS:A survey was performed on the fertility of 164 male renal transplant recipients who underwent a long-term treatment with cyclosporine A (CsA),...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2009.10.001
更新日期:2009-12-01 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:AIMS:Chronic renal allograft loss is still an unsolved problem in kidney transplantation. We evaluated the impact of FTY720, a S1P receptor agonist, known to deplete lymphocytes from the peripheral blood by sequestering them into lymph nodes and Peyer's patches, on blood lymphocytes and graft infiltrating cells in a ra...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2016.01.003
更新日期:2016-03-01 00:00:00
abstract::HMG-CoA reductase inhibitors, or statins, are effective lipid lowering agents, extensively used in medical practice. Statins have never been shown to be involved in the immune response, although few clinical reports have suggested a better outcome of cardiac transplantation in patients under pravastatin therapy. Major...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/s0966-3274(02)00030-8
更新日期:2002-05-01 00:00:00
abstract::The effect of blocking the expression of the mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in a graft by an antibody, and immunohistochemical changes in the graft were monitored, using a rat small intestinal transplantation model. Dark Agouti (DA) rat small intestines were heterotopically transplanted into Lew...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2007.01.011
更新日期:2007-06-01 00:00:00
abstract:OBJECTIVE:The immunomodulator, FTY720, lowers the peripheral lymphocyte count (PLC) by inducing migration of circulating lymphocytes to secondary lymphoid organs. We investigated the efficacy of mono- vs. combined-FTY720/CsA therapy on graft survival (GS) and on lowering the PLC in a solid organ and a skin graft model,...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(01)00031-4
更新日期:2001-02-01 00:00:00
abstract::There have been several reports that xeno-MHC-restricted T-cells have a cytotoxic function through a direct xenoantigen recognition, but yet no report that they have a helper function. Previously we showed that both xeno-MHC-restricted CD4(+) and CD8(+) T-cells recognized xenoantigens directly in a mouse anti-rat comb...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/S0966-3274(02)00158-2
更新日期:2003-04-01 00:00:00
abstract::Adoptive cell therapies involving cell manipulation to achieve tolerance are increasingly being studied in animal models and in human trials. We have demonstrated that the specific removal of allo-stimulated dividing cells (or "pruning") promotes long-term allograft survival across a major MHC mismatch in transplant m...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2014.03.002
更新日期:2014-05-01 00:00:00
abstract::Mycophenolate mofetil (MMF) a potent immunosuppressive agent, has recently been approved for clinical use (CellCept) in renal transplant patients in combination with cyclosporine (CsA). With the expanded use of tacrolimus (Prograf) as well in renal transplant patients, there is a lack of pharmacokinetic studies clarif...
journal_title:Transplant immunology
pub_type: 临床试验,杂志文章
doi:10.1016/s0966-3274(97)80042-1
更新日期:1997-09-01 00:00:00
abstract::Mixed lymphocyte reaction (MLR) assays were performed serially over 24 months in 19 first cadaver renal transplant recipients. Immunosuppression consisted of cyclosporine, methylprednisolone and azathioprine. Cyclosporine was withdrawn at 6 months postoperatively. The MLR reactivity gradually decreased over the first ...
journal_title:Transplant immunology
pub_type: 临床试验,杂志文章
doi:10.1016/s0966-3274(98)80016-6
更新日期:1998-12-01 00:00:00
abstract::Type 1 diabetes is one of the more costly chronic diseases of children and adolescents throughout North America and Europe, exhibiting an average estimated prevalence rate of nearly 0.2%. It occurs in genetically predisposed individuals when the immune system attacks and destroys specifically the insulin-producing bet...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/j.trim.2003.12.011
更新日期:2004-04-01 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:BACKGROUND:Peroxisome Proliferator-Activated Receptor gamma (PPARgamma) is a nuclear receptor that regulates the transcription of genes associated with lipid and glucose metabolism. Recently, it has been shown that PPARgamma modulates the activity of T cells, resulting in inhibition of T cell proliferation and IL-2 rel...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2007.03.003
更新日期:2007-07-01 00:00:00
abstract:BACKGROUND:Molecules of the innate immune response are increasingly recognized as important mediators in allograft injury during and after kidney transplantation. We therefore aimed to establish the relationship between the expression of these genes at implantation, during an acute rejection (AR) and on graft outcome. ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2018.02.009
更新日期:2018-06-01 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: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...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2012.10.004
更新日期:2012-12-01 00:00:00
abstract::Data binding the expression of Toll-like 4 receptor (TLR4ex), transplanted kidney function, and the cause of pre-transplant end-stage renal disease are scarcely available. OBJECTIVE:To investigate the relationship between pre-transplant chronic interstitial nephritis (CIN), TLR4ex and transplanted kidney function. M...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2020.101319
更新日期:2020-10-01 00:00:00
abstract::This study provides data on HLA-A, -B, and -DRB1 frequencies among 861 end-stage renal disease (ESRD) patients from Croatia and estimates the benefit of the kidney exchange program by comparing HLA distribution and assessing HLA mismatches (MMs) within a group of ESRD patients who received kidney grafts from 707 cadav...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2020.101318
更新日期:2020-10-01 00:00:00
abstract::Rabbit anti-rat thymoglobulin (rATG) administered to donors with brain death (BD) may improve organs quality. We explored the effects of rATG administered to BD donors in the histology of heart, lungs and small bowel in a rat experimental model. Animals were randomly assigned to 3 groups: V (n=5) no BD, 2h ventilation...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2013.04.002
更新日期:2013-06-01 00:00:00
abstract::Although the clinical significance of anti-HLA antibodies in heart and lung transplantation is less well studied than in renal transplantation, several studies have shown that heart and lung recipients transplanted in the presence of donor-specific antibodies are at increased risk for early acute rejection and have a ...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/j.trim.2004.01.005
更新日期:2004-06-01 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::Clinical ophthalmologists are highly successful in grafting allogeneic corneas onto healthy eye graft beds--only a small percentage are rejected. By contrast, a high percentage of allografts are rejected when grafted into vascularized or '"high-risk' recipient eyes. The following experiments test the hypothesis that d...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(96)80034-7
更新日期:1996-03-01 00:00:00
abstract::The induction of antigen-specific T cell tolerance and its maintenance in the periphery are critical for the immune system to prevent autoaggressive immune responses. Our current state of knowledge about the immunoregulatory mechanisms responsible for T cell tolerance in the periphery offers new possibilities for immu...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/S0966-3274(03)00057-1
更新日期:2003-07-01 00:00:00
abstract:BACKGROUND:Acute rejection is a major obstacle in patients with prolonged ischemia in deceased-donor renal transplantation. Chemokines and their receptors play a critical role in leukocyte trafficking, resulting in allograft rejection; therefore, the role of chemokine receptor CXCR3 in acute rejection induced by prolon...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2015.08.001
更新日期:2015-10-01 00:00:00