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. Combined therapy of ISD, NK-cells and/or MSCs is used in clinical practice. Here, we examined the effects of MSCs and selected ISD (tacrolimus, cyclosporin A, mycophenolic acid, dexamethasone) treatment on early NK-cell activation. We assessed STAT4 and STAT5 phosphorylation triggered by IL-12 and IL-2, respectively. Furthermore, we determined IFNγ, perforin production and the expression pattern of selected NK-cell receptors. Of all drugs tested, only dexamethasone inhibited NK-cell STAT4 and STAT5 phosphorylation. All ISD, with the exception of MPA, significantly inhibited IFNγ, and only dexamethasone inhibited upregulation of early activation markers CD69 and CD25 (IL-2 condition only). MSCs inhibited IL-2 induced NK cell STAT5 phosphorylation, IFNγ production and CD69 upregulation, and IL-12 induced IFNγ and perforin production. While MSCs mediated inhibition of CD69 expression was cell contact dependent, inhibition of IFNγ and perforin production, as well as STAT5 phosphorylation was cell-contact independent. Importantly, dexamethasone augmented MSCs mediated inhibition of both IL-12 and IL-2 induced CD69 expression and IFNγ production, as well as IL-2 induced STAT5 phosphorylation. Taken together, these novel insights may help the design of future NK-cell and MSCs based immunotherapy.
journal_name
Transpl Immunoljournal_title
Transplant immunologyauthors
Michelo CM,Fasse E,van Cranenbroek B,Linda K,van der Meer A,Abdelrazik H,Joosten Idoi
10.1016/j.trim.2016.04.008subject
Has Abstractpub_date
2016-07-01 00:00:00pages
1-9eissn
0966-3274issn
1878-5492pii
S0966-3274(16)30030-2journal_volume
37pub_type
杂志文章abstract::Alloreactive T-cell responses directed against minor histocompatibility (H) antigens, which arise from diverse genetic disparities between donor and recipient outside the MHC, are an important cause of rejection of MHC-matched grafts. Because clinically significant responses appear to be directed at only a few antigen...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2013.10.005
更新日期:2013-12-01 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::Dendritic cells (DC) are considered to be the major cell type responsible for induction of primary immune responses. While they have been shown to play a critical role in eliciting allosensitization via the direct pathway, there is evidence that maturational and/or activational heterogeneity between DC in different do...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(00)00010-1
更新日期:2000-03-01 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::Calcineurin a calmodulin-dependent phosphatase plays a critical role in calcium-dependent activation of T-lymphocytes and is the major target for the inhibitory actions of the immunosuppressive drugs Tacrolimus (FK506) and Cyclosporin A (CsA). Calcineurin is a dimeric protein consisting of distinct A (catalytic) and B...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(00)00020-4
更新日期:2000-06-01 00:00:00
abstract::Persistent rejection in the face of treatment and multiple episodes of rejection are associated with the development of chronic rejection and graft loss in solid organ transplantation. The factors that create an environment for rejection that persists in the face of treatment are as yet not understood. The objective o...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2004.11.001
更新日期:2005-03-01 00:00:00
abstract:OBJECTIVE:Acute rejection is a major cause of morbidity and mortality after solid organ transplantation. Therefore, optimizing treatment strategies and improving curative effect is urgent and necessary. Reliable biomarkers for acute rejection and the underlying molecular mechanisms remain to be determined. METHODS:In ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2020.101320
更新日期:2020-10-01 00:00:00
abstract::In recent years, the utility of vascular complement factor 4d (C4d) deposition as diagnostic tool for antibody mediated rejection (AMR) after lung transplantation, has become a controversial issue. We aimed to pinpoint the problematic nature of C4d as biomarker with a simple experiment. We quantified C4d in broncho-al...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2020.101352
更新日期:2021-02-01 00:00:00
abstract::The novel immunosuppressive agents malononitrilamides (MNA) 279 and 715 are derivatives of A77 1726, the primary metabolite of leflunomide. The effects of these agents have been previously demonstrated in rat skin and cardiac allo- and xenotransplant models. The aim of this study was to evaluate the combination of MNA...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(99)80036-7
更新日期:1999-09-01 00:00:00
abstract::Tissue eosinophils have been previously implicated in allograft rejection and graft loss. The aim of this study was to evaluate the role of eosinophils in acute renal allograft rejection. Data from 71 patients with 114 renal biopsies with acute allograft rejection were compared with those from 26 controls. The median ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/0966-3274(94)90076-0
更新日期:1994-01-01 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: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::Regulatory T cells, especially CD4(+)CD25(+) regulatory T cells are critical regulators of immune tolerance in humans and mice. Mice with humanized immunity have been developed by various transplantation strategies of human tissues or cells related to immunity, which are being extensively applied in biomedical researc...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2011.08.003
更新日期:2011-12-01 00:00:00
abstract::The interaction of antibodies with cell surface antigens may induce redistribution of immune complexes, followed by antigen depletion, with increased resistance to injurious effect of antibody and complement (antigenic modulation). Human natural antibodies to Gal alpha 1,3Gal beta 1,4GlcNAc-R (alpha Gal) epitopes expr...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(99)80026-4
更新日期:1999-06-01 00:00:00
abstract:BACKGROUND:Transforming growth factor beta-1(TGFB1) is involved in the acute rejection (AR) episodes of solid organ transplant recipients. However, results from published studies on the association between donor/recipient TGFB1 +869T/C polymorphism and AR risk are conflicting and inconclusive. METHODS:PUBMED, EMBASE, ...
journal_title:Transplant immunology
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.trim.2014.01.001
更新日期:2014-03-01 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: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: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::Calcineurin inhibitors (CNI) cyclosporine (Csa) and tacrolimus (Tac) are now first intention immunosuppressive drugs in renal transplantation. However, although these treatments are effective for preventing allograft rejection, they are nephrotoxic: they can cause chronic renal dysfunction and degradation of renal gra...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2008.09.002
更新日期:2008-11-01 00:00:00
abstract:BACKGROUND:Peripheral blood CD4+ T cell adenosine triphosphate (ATP) release has been reported to be an adjunct tool to evaluate global cellular immune response in solid-organ transplant recipients. However, the correlation between the ATP level and rejection was controversial. The aim of this prospective clinical stud...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2013.10.008
更新日期:2014-01-01 00:00:00
abstract::Gene polymorphisms of cytotoxic T lymphocyte associated antigen 4 (CTLA4) play an influential role in the graft rejection and long-term clinical outcome of organ transplantation. We investigated the associations of five CTLA4 single nucleotide polymorphisms (SNPs) (rs733618T/C, rs4553808A/G, rs5742909C/T, rs231775G/A,...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2012.02.005
更新日期:2012-06-01 00:00:00
abstract::Models of severe combined immuno-deficient (SCID) mice reconstituted with a competent human immune system represent a valuable tool for the study of human immune responses in vivo. Reconstitution with human cells can be achieved using large numbers of peripheral blood lymphocytes, but levels of engraftment are poor an...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2005.07.002
更新日期:2005-12-01 00:00:00
abstract::TIRC7 delivers essential signals during immune activation as antibodies targeting TIRC7 inhibit lymphocyte proliferation and Th1 cytokine expression in vitro and prolonged kidney and heart allograft survival in vivo. Immunohistochemical analysis of biopsy specimens from human renal allografts undergoing rejection desp...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2006.09.027
更新日期:2006-11-01 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:BACKGROUND:Pigs are frequently used as animal models for experiments in the surgical field, including allo- and xeno-transplantation. Regeneration studies, including studies dealing with human- and monkey-induced pluripotent stem cells (iPSC), have gradually progressed, with pigs sometimes being used as the scaffold. H...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2016.12.002
更新日期:2017-02-01 00:00:00
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::Desensitization (DS) is widely used to decrease PRA in solid organs transplant candidates (TC). Various numbers of cycles of DS are required to reduce or eliminate donor specific antibodies (DSA). The goal of this study was to investigate if there was a correlation between polymorphism (PM) of some cytokine genes and ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2009.03.002
更新日期:2009-07-01 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::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:INTRODUCTION:Glutathione (GSH) is added to University of Wisconsin (UW) organ preservation solution to protect against oxidative stress. This study assesses the effect of GSH-supplementation on endothelial function in tissues subjected to cold ischaemia and compares its effects to a mono-ethyl ester equivalent (GSH-MEE...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2007.06.002
更新日期:2007-11-01 00:00:00