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 immunosuppressive effect of MSCs, we assessed the interaction of MSCs and common clinical immunosuppresants (MMF, sirolimus [Srl], and ciclosporin A [CiA]) in a parent-into-F1 cell transfer model. In this model, the transfer of parental strain T cells into semi-allogeneic F1 recipients induces a graft-versus-host reaction (GvHR). Re-isolated CFSE-labelled T lymphocytes were analyzed by flow cytometry. These findings were compared to a fully allogeneic heart transplantation model. RESULTS:We found that MSC treatment alone had no significant effect on allograft survival of heterotopic heart grafts. However, MSCs combined with short-term mycophenolate mofetil (MMF) significantly prolonged graft survival. Quantitative analysis of three different MSC - drug combinations in the F1 model revealed, that only the MSC-MMF combination led to a super-additive immunosuppressive effect. We also investigated the effect of MMF and CiA on IFNγ production of stimulated lymphocytes and found that MMF left the expression of IFNγ unaffected, whereas CiA completely abolished the production of IFNγ. CONCLUSION:Our data show that the type of concurrent immunosuppression strongly influences the immunosuppressive effect of MSC, most likely through differential secretion of IFNγ. A regimen combining MSCs and MMF was most immunosuppressive.
journal_name
Transpl Immunoljournal_title
Transplant immunologyauthors
Eggenhofer E,Renner P,Soeder Y,Popp FC,Hoogduijn MJ,Geissler EK,Schlitt HJ,Dahlke MHdoi
10.1016/j.trim.2011.06.002subject
Has Abstractpub_date
2011-09-01 00:00:00pages
141-7issue
2-3eissn
0966-3274issn
1878-5492pii
S0966-3274(11)00062-1journal_volume
25pub_type
杂志文章abstract：:Pancreas grafts do not survive for lengthy periods, especially in a high-responder rat combination. Recent data indicated that a combined spleen/pancreas graft protects against acute graft rejection and induces donor-specific tolerance. In this study, we performed a combination spleen/pancreas transplantation using hi...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/s0966-3274(01)00049-1
更新日期：2001-10-01 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：: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: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：: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：:Experimental data show that relatively low concentrations of 15-deoxyspergualin (DSG) inhibit the induction of cytotoxic T lymphocytes (CTL) and the generation of antibody-producing cells. Considerably higher concentrations of DSG are required to inhibit proliferative responses. In this in vitro study, the effects of ...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/s0966-3274(96)80007-4
更新日期：1996-06-01 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 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：: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：:It is known that the expression level of the heat shock protein (HSP) is elevated in allograft tissues, but the specific role of the HSP in the acute rejection has not been elucidated. This study aims to determine how and when the HSP72 molecule works immunologically in the process of acute allograft rejection from a ...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/j.trim.2004.08.003
更新日期：2004-12-01 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：: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：: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：BACKGROUND:B cell depletion by anti-CD20 antibody is used in desensitization protocols and for treatment of antibody-mediated rejection (AMR). However, little is known about the efficacy and the mechanism(s) of action. METHODS:A mouse model of HLA sensitization was used to study the effectiveness of anti-CD20 treatmen...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/j.trim.2008.05.004
更新日期：2008-07-01 00:00:00
abstract：:Alloreactivity probably involves T cell recognition of peptides bound to allogeneic HLA molecules. In order to study whether T cells recognizing common viral antigens presented by self HLA molecules also recognize some allogeneic HLA molecules we generated T lymphocyte clones (TLC) specific for herpes simplex virus (H...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/0966-3274(93)90005-s
更新日期：1993-01-01 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：: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：BACKGROUND:The potential of mesenchymal stem cells (MSCs) for immunosuppression has been tested in transplantation, but its mechanisms are not fully understood. This study investigated the role of MSC-expressing B7-H1 in the induction of immune tolerance to cardiac allografts by the combination therapy of MSCs and rapa...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/j.trim.2014.06.005
更新日期：2014-08-01 00:00:00
abstract：:The myeloid-related proteins 8 and 14 exist as a dimeric complex (MRP 8/14) and serve as early and highly specific markers for inflammatory processes, such as allograft rejection and non-viral (bacterial or fungal) infections. An elevated procalcitonin (PCT) concentration in serum also serves as a diagnostic indicator...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/j.trim.2007.10.004
更新日期：2008-02-01 00:00:00
abstract：:Cytokines are important factors determining the outcome of transplantation since host ability in cytokine production may be affected by cytokine gene polymorphisms. The aim of the present study was to investigate the effect of IL-17, IL-23R and IL-21 gene polymorphisms in the outcome of kidney transplantation. A total...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/j.trim.2013.09.006
更新日期：2014-01-01 00:00:00
abstract：BACKGROUND:Conditioning chemotherapies for hematopoietic stem cell transplantation (HSCT), especially those that include total body irradiation, can result in serious complications such as graft-versus-host disease (GVHD). Human leukocyte antigen G (HLA-G) is a non-classical class I molecule with multiple immunoregulat...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/j.trim.2018.12.001
更新日期：2019-04-01 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 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：: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 status of "partial" tolerance to organ allografts versus the status of complete tolerance is the main topic of this paper. Progress made in immunosuppression, particularly by use of various lymphocyte depleting agents for "induction therapy", seems to favor the subsequent development of T cells with suppressor/reg...
journal_title：Transplant immunology
pub_type： 杂志文章,评审
doi：10.1016/j.trim.2004.05.002
更新日期：2004-09-01 00:00:00
abstract：:Previously, we established a murine model, that involves the engraftment of fully allogeneic T cell depleted donor bone marrow cells in sublethally irradiated and single dose anti-CD3 treated recipient mice. These mice developed permanent stable multilineage mixed chimerism and donor-specific tolerance without graft-v...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/S0966-3274(02)00157-0
更新日期：2003-07-01 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：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：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：: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
