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 survival. Although this is a well known aspect, the mechanisms of MHC-driven graft damage and the impact of other immunological factors leading to chronic rejection are poorly understood. In patients it is impossible to study MHC mismatches without considering non-MHC differences. Further more common animal models for chronic rejection are all characterized by non-MHC as well as MHC disparities. To exclusively study MHC mediated immunoresponses we established a rat model of renal transplantation using congenic rat strains differing in their entire MHC class I and class II, but sharing the genetic background of the LEW rat. After an initial short term of immunosuppression all animals developed renal impairment with severe albuminuria. Half of the animals died of renal failure in week 7 to 14 and showed pathological characteristics of chronic allograft damage including IF/TA and severe glomerulopathy. The majority of these recipients developed circulating donor-specific MHC alloantibodies. Allografts were significantly infiltrated with T-cells, macrophages and NK-cells. We established a MHC congenic rat model to investigate immunological mechanisms of chronic renal allograft rejection exclusively induced by a complete MHC mismatch. We demonstrated humoral as well as cellular immunoresponses leading to chronic allograft loss in 50% of animals.
journal_name
Transpl Immunoljournal_title
Transplant immunologyauthors
Poehnert D,Broecker V,Mengel M,Nashan B,Koch Mdoi
10.1016/j.trim.2009.09.007subject
Has Abstractpub_date
2010-02-01 00:00:00pages
137-43issue
3-4eissn
0966-3274issn
1878-5492pii
S0966-3274(09)00100-2journal_volume
22pub_type
杂志文章abstract::Complex polygenic and multifactorial diseases remain a challenge for human geneticists. Here we aim to remind basic definitions of multifactorial diseases and the genetic related concepts underlying classical methods. Knowledge on pathophysiological process and the genetic information available conditions the design o...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/j.trim.2005.03.015
更新日期:2005-08-01 00:00:00
abstract::We suggest that surveillance for squamous cell cancer might be particularly useful for transplant patients receiving statin therapy. We recommend that development of non melanoma skin cancer should be specified as a secondary endpoint in future large endpoint statin trials, and suggest that in transplant patients the ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2010.06.001
更新日期:2010-08-01 00:00:00
abstract::Previous work on the facilitation of xenogeneic and allogeneic bone marrow engraftment in irradiated mice and dogs with transferrins allowed the development of a model for induction of an apparently durable state of immunological unresponsiveness or 'tolerance' in chemically immunosuppressed mice. The system is based ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(96)80051-7
更新日期:1996-12-01 00:00:00
abstract::The containment of direct and indirect recognition of donor alloantigens by enhancement of the number and activity of regulatory T cells (Tregs) has been one of the promising approaches to achieve transplant tolerance. Two major methods, dendritic cell (DC) and anti-CD3/CD28 antibodies (Abs) have been introduced for e...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2009.07.004
更新日期:2009-12-01 00:00:00
abstract:BACKGROUND:The transcription factor Forkhead Box P3 (FoxP3) is a marker of regulatory T cells (Tregs) - a subset of T cells known to suppress a wide range of immune responses. These cells are considered to be pivotal for the induction of tolerance to donor antigens in human allografts. We aimed to correlate the number ...
journal_title:Transplant immunology
pub_type: 临床试验,杂志文章
doi:10.1016/j.trim.2013.08.002
更新日期:2013-12-01 00:00:00
abstract::Upon activation, T cells express CD40L, a member of the TNF cytokine superfamily, which serves as a ligand for CD40 on antigen presenting cells, including dendritic cells, B cells, and macrophages. While initial studies on the function of CD40 focused its role in the regulation of B cell activation, more recent studie...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(00)00026-5
更新日期:2000-11-01 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::The mechanisms by which alloreactive memory T-cells are generated in non-sensitized individuals have begun to be elucidated. It is generally accepted that a very high level of crossreactivity is an essential feature of the T-cell receptor. Indeed it has recently been shown that alloreactivity from viral specific memor...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/j.trim.2010.06.008
更新日期:2010-08-01 00:00:00
abstract:BACKGROUND:Results from published studies on the association of donor or recipient IL-6 -174G/C (rs1800795) polymorphism with acute rejection (AR) of renal allograft are conflicting. We performed a meta-analysis to estimate the possible association. METHODS:Studies were identified by searching PUBMED and EMBASE until ...
journal_title:Transplant immunology
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.trim.2011.10.003
更新日期:2012-01-01 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::TCR-beta (T cell receptor-beta chain) transgenic mice have altered lymphocyte development. TCR-beta transgenic mice are hyporesponsive to alloantigens in vivo and are deficient in gamma delta T cells. In order to begin a study of the relationship between a deficiency of alloreactive gamma delta cells and the defective...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/0966-3274(94)90063-9
更新日期:1994-09-01 00:00:00
abstract::Adenovirus-mediated CTLA4Ig gene transfer has been reported to enhance graft survival in several rodent transplantation models. In this study, we investigated the efficacy of ex vivo and systemic transfer of the CTLA4Ig gene by adenoviral vectors in pancreatic islet allo-transplantation. Islet grafts from BN rats were...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/S0966-3274(02)00153-3
更新日期:2003-01-01 00:00:00
abstract::The effects of FK506, and TAK-779, antagonists of CCR5 and CXCR3, were investigated using a rat intestinal transplantation model. Small intestines from DA rats were heterotopically transplanted into LEW rats. The recipients were treated with FK506 (1mg/kg/day, day 0-5) and TAK-779 (10mg/kg/day, day 0-10). Graft surviv...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2011.04.003
更新日期:2011-07-01 00:00:00
abstract::The immune system is an adaptive defense system capable of specifically recognizing and eliminating an apparently limitless variety of foreign invaders. This highly specific response is provided by T and B lymphocytes. The enormous diversity of the antigen-specific receptors on these cells is generated by random rearr...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/s0966-3274(02)00056-4
更新日期:2002-08-01 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::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::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: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
abstract::Naturally occurring antibodies to the galactose alpha1,3 galactose (alpha gal) epitope expressed on xenogeneic grafts are a major barrier to organ transplantation in humans. Porcine small intestinal submucosa (SIS) expresses the alpha gal epitope and is currently being used as a bioscaffold for tissue remodeling. To e...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(01)00044-2
更新日期:2002-06-01 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:BACKGROUND:Antibody-mediated rejection (ABMR) is the leading cause of kidney graft loss worldwide. Criteria for acute humoral rejection (currently labeled active humoral rejection) established by the 2007 Banff classification are highly specific but lack sensitivity. Modifications to the Banff classification were intro...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2018.08.008
更新日期:2018-12-01 00:00:00
abstract::Stem cell transplantation (SCT) has emerged to be an appealing tool for repair medicine. In the treatment of ischemic heart diseases, SCT will be of great help because it is capable of replacing scar with new myocardial tissue. Among the many candidate cell lines for SCT, embryonic stem cells (ESCs) have their unique ...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/j.trim.2007.05.003
更新日期:2007-11-01 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::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:BACKGROUND:Although high-mobility group box-1 (HMGB1), which is a nuclear protein, was reported to enhance the allogeneic responses in transplantation, the effect of HMGB1 on bronchiolitis obliterans syndrome (BOS) is unknown. METHODS:A murine heterotopic tracheal transplantation model was used. Protein concentrations...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2018.11.007
更新日期:2019-04-01 00:00:00
abstract::Graft-vs.-host disease (GVHD) caused by immunologic activated cells remains a real problem in human allogeneic hematopoetic stem cell transplantation. Mesenchymal stem cells (MSCs) play some important roles on immunomodulatory. We developed a parent-into-F1 model of acute GVHD to evaluate the mechanisms involved in im...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2009.08.002
更新日期:2009-12-01 00:00:00
abstract:BACKGROUND:Tim-3 was recently described as a Th1-specific molecule, participating in the regulation of immune responses and in the induction of allograft tolerance. Here, we studied Tim-3 mRNA expression together with molecular markers of T-cell activation and cytotoxicity, in rejected human kidney grafts. METHODS:Twe...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2006.11.003
更新日期:2007-04-01 00:00:00
abstract::Using specific cell surface receptors lymphocytes continuously sample their environment. Maturation of the immune system and initiation of a specific immune response rely on an array of extracellular cues that elicit complex intracellular biochemical signals. Essential molecules involved in signal transduction from im...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/s0966-3274(02)00009-6
更新日期:2002-05-01 00:00:00
abstract::Although natural killer cells lyse targets without pre-sensitization, and in an MHC-unrestricted manner, they can also respond to healthy allogeneic cells of different MHC type. Such alloreactivity is a consequence of NK cells using clonally distributed, inhibitory MHC class I receptors to achieve tolerance to healthy...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/j.trim.2006.09.022
更新日期:2006-12-01 00:00:00