Abstract:
:The means by which methotrexate (MTX) mediates immunosuppression at low doses remains to be elucidated. MTX has been shown to inhibit the adherence of neutrophils and fibroblasts to endothelial cells in vitro. The hypothesis that MTX treatment may affect cellular adherence by downregulating cell adhesion molecule expression formed the rationale for these studies. Previous studies of rat cardiac transplant recipients in our laboratory demonstrated that low-dose MTX treatment alone significantly inhibits the expression of the leucocyte beta 2 integrin subunit, CD18. These investigations have addressed whether low-dose MTX treatment might also affect the expression of the beta-integrin counter-receptor, ICAM-1, a cell adhesion molecule which may be induced on endothelial cells during an immune response. The degree to which low-dose cyclosporine A and low-dose MTX treatment alone, and in combination, impact cell adhesion molecule expression has been studied in Brown Norway (BN) to Lewis (Lew) rat accessory cervical heart allografts. According to both Northern blot and immunohistochemical analysis, ICAM-1 expression was upregulated in graft regional lymph nodes and in the spleen of untreated cardiac allograft recipients within 6 h post-transplantation. Despite induction of VCAM-1 expression, ICAM-1 expression remained low or undetectable in cardiac allograft tissue as measured both by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemical analysis. These data suggest that ICAM-1 may function in leucocyte trafficking through lymphoid organs, such as the lymph nodes and spleen, but not directly in graft leucocyte recruitment during BN to Lew rat cardiac allograft rejection. Despite prolonged allograft survival with cyclosporine A alone and combination cyclosporine A/MTX, these treatments did not result in diminished steady-state ICAM-1 mRNA levels in regional lymph nodes or spleen of cardiac allograft recipients. MTX treatment alone, however, substantially diminished ICAM-1 expression in allograft recipient lymphoid tissues. These studies demonstrate for the first time in vivo using a rat model of acute allograft rejection that MTX but not cyclosporine treatment downregulates cell adhesion molecule expression. Low-dose MTX treatment alone, however, is not sufficient to result in prolonged BN to Lew rat cardiac allograft survival. The means by which combination low-dose cyclosporine A and MTX treatment results in prolonged rat cardiac allograft survival over low-dose cyclosporine treatment alone remain(s) to be clarified.
journal_name
Transpl Immunoljournal_title
Transplant immunologyauthors
Ciesielski CJ,Pflug JJ,Mei J,Piccinini LAdoi
10.1016/s0966-3274(98)80026-9subject
Has Abstractpub_date
1998-06-01 00:00:00pages
111-21issue
2eissn
0966-3274issn
1878-5492pii
S0966-3274(98)80026-9journal_volume
6pub_type
杂志文章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: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 AND PURPOSE:Since the Fas/Fas Ligand (FasL) interaction has been recognized as an apoptotic pathway, it eliminates the activated T cells and promotes the survival of grafts. In this study, the effect of FasL transfection of pig chondrocytes on allogeneic transplantation was examined in vitro and in vivo. ME...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2008.02.001
更新日期:2008-05-01 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:BACKGROUND:The Fischer-to-Lewis (LEW) rat model of kidney transplantation is a widely accepted and well-characterized model of chronic rejection. In contrast to transplantation in a clinical setting, however, the absence of treatment with immunosuppressants and only minor mismatch of major histocompatibility complexes ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2016.08.002
更新日期:2016-09-01 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::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::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::Human anti-pig antibodies were obtained by perfusing pig hearts (n = 4) and kidneys (n = 8) with human AB or O plasma followed by elution with 3 M NaSCN. The antibodies were screened against a panel of 132 synthetic carbohydrates conjugated to bovine serum albumin using an enzyme-linked immunoassay. An anti-immunoglob...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/0966-3274(93)90047-c
更新日期:1993-01-01 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
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::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::Organ transplantation is an effective way to treat many end-stage diseases. In order to overcome post-transplant rejection, immunosuppressive agents have been widely used, but the long-term survival of transplanted organs still has not been achieved in the clinic. For decades, tolerance is the "holy grail" that transp...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/j.trim.2019.101250
更新日期:2020-02-01 00:00:00
abstract::A rapid and robust limiting dilution assay was developed to measure the frequency of donor-reactive, IL-2 (interleukin 2) producing, helper T lymphocytes in the peripheral T cell population of organ allograft recipients. The IL-2 bioassay was performed using two methodologies to assess the response of CTLL-2 indicator...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/0966-3274(94)90006-x
更新日期:1994-12-01 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::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:Donor passenger leukocytes (DPLs) that migrate after organ transplantation stimulate the recipient immune system and normally cause rejection and graft vs. host reaction. However, DPLs also contribute to the unresponsiveness to the donor organ. The quantity and quality of these migrating cells are considered...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2003.10.001
更新日期:2004-01-01 00:00:00
abstract::Application of mesenchymal stromal cells (MSCs) has been proposed for solid organ transplantation based on their potent immuno-modulatory effects in vitro and in vivo. We investigated the potential of MSCs to improve acceptance of kidney transplants in an MHC-incompatible rat model including isogeneic kidney transplan...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2013.08.004
更新日期:2013-12-01 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:BACKGROUND:Our laboratory has demonstrated that xenogeneic porcine thymus tissue grafted in thymectomized (ATX) and T cell-depleted mice induces donor-specific tolerance. Recipient thymectomy is essential for the success of tolerance induction. In contrast, studies in pigs grafted with non-vascularized allogeneic class...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2005.04.004
更新日期:2005-10-01 00:00:00
abstract::Autoimmune diseases are the result of an interplay between predisposing genes and triggering environmental factors, leading to loss of self-tolerance and an immune-mediated destruction of autologous cells and/or tissues. Genes in the HLA complex are among the strongest predisposing genetic factors. The HLA complex gen...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/j.trim.2005.03.021
更新日期:2005-08-01 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: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::Previously, we developed a well-tolerated single-day protocol for induction of stable multilineage chimerism and permanent donor-specific tolerance across major histocompatibility complex (MHC) barriers, with preservation of the host's normal immune responses. In our murine model, recipient mice were treated with a si...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(98)80039-7
更新日期:1998-09-01 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::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:While acute neurotoxic side effects of calcineurin inhibitors (CNI) are well-known, data upon long-term effects on brain structure and function are sparse. We hypothesize that long-term CNI therapy affects the neuroimmune system, thereby, increasing the risk of neurodegeneration. Here, we measured the impact...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2019.101248
更新日期:2020-02-01 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::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: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