Abstract:
BACKGROUND:Monocarboxylate transporter (MCT)-1, a member of a family of molecules, transports monocarboxylates such as lactate. Inhibiting MCT-1 leads to long-term graft survival in rodent heart transplantation and induces tolerance. We evaluated an MCT-1 inhibitor, AS2495674, in a rat heart transplant model and analyzed its underlying mechanism. METHODS:AS2495674 was tested on rat lymphocytes to determine its effect on lactate accumulation, proliferation, and immunoglobulin production. The effect of AS2495674 on graft survival was tested on the Brown Norway to Lewis rat strain combination with a second heart transplantation to test donor-specific suppression. Histology and ex vivo analyses were done to examine the AS2495674 effects on the immune response. RESULTS:In vitro, AS2495674 resulted in lactate accumulation, inhibited lymphocyte proliferation, and prevented immunoglobulin production. AS2495674 induced long-term allograft survival with little evidence of chronic rejection and induced donor-specific suppression. Evaluation of the allograft and peripheral T lymphocytes from the AS2495674 group compared with that of vehicle showed (1) decreased donor-specific T lymphocyte response, (2) more forkhead box P3+ (Foxp3+) and CD45RA+ cells in the allograft, (3) higher gene expression of chemokines and chemokine receptors in the allograft, and (4) preferential inhibition of Foxp3(-) cells with little or no effect on Foxp3+ cells. CONCLUSIONS:AS2495674 prevents acute rejection, reduces features of chronic rejection, and induces tolerance. Our data suggest that the mechanism of AS2495674 involves generating a tolerogenic graft environment by preferentially targeting T effector cells while sparing the generation of T regulatory cells.
journal_name
Transplantationjournal_title
Transplantationauthors
Cho KS,Yamada T,Wynn C,Behanna HA,Hong IC,Manaves V,Nakanishi T,Hirose J,Abe Y,Jiang H,Tamura K,Saita Ydoi
10.1097/TP.0b013e3181ff8818subject
Has Abstractpub_date
2010-12-27 00:00:00pages
1299-306issue
12eissn
0041-1337issn
1534-6080journal_volume
90pub_type
杂志文章相关文献
TRANSPLANTATION文献大全abstract:BACKGROUND:There are limited data on the outcome of transplant recipients with familial Mediterranean fever (FMF)-associated AA amyloidosis. The aim of the present study is to evaluate demographic, clinical, laboratory, and prognostic characteristics and outcome measures of these patients. METHODS:Eighty-one renal tra...
journal_title:Transplantation
pub_type: 杂志文章,多中心研究
doi:10.1097/TP.0000000000003043
更新日期:2020-08-01 00:00:00
abstract::The histopathological features of chronic rejection and its initiation were assessed using rat heterotopic heart transplantation and retransplantation models. Fully allogeneic or minor, non-MHC antigen-mismatch heart grafts transplanted into recipient rats treated with a short course of FK506 showed long-term survival...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199511270-00002
更新日期:1995-11-27 00:00:00
abstract::Nonadherence to immunosuppressants in renal transplant recipients is a major factor affecting graft survival, but it is difficult to detect accurately in clinical practice. Adherence was measured in 153 adult renal transplant recipients using self-report questionnaires and interview, clinician rating, and cyclosporine...
journal_title:Transplantation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/01.tp.0000110412.20050.36
更新日期:2004-03-15 00:00:00
abstract::T cells must be activated before they can elicit damage to allografts, through interaction of their T cell receptor (TCR) with peptide-MHC complex and through accessory molecules. Signaling through accessory molecules or costimulatory molecules is a critical way for the immune system to fine tune T cell activation. An...
journal_title:Transplantation
pub_type: 杂志文章,评审
doi:10.1097/TP.0b013e31826d4672
更新日期:2013-02-27 00:00:00
abstract:BACKGROUND:Although human herpesvirus (HHV)-6 is now recognized as a frequent pathogen after transplantation, the real impact of this infection in patients undergoing transplantation remains unclear. METHODS:During 27 months, 30 consecutive heart-lung- and lung-transplant recipients were included on the day of transpl...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.TP.0000058809.42027.66
更新日期:2003-06-27 00:00:00
abstract:BACKGROUND:Urolithiasis occurs in approximately 6% of adult kidney transplant (KTx) recipients. Limited data are available on urolithiasis after pediatric KTx. We report the incidence, management of, and risk factors for stone development in children after KTx. METHODS:We reviewed the medical records of 399 children w...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.tp.0000139543.56886.de
更新日期:2004-11-15 00:00:00
abstract::Isolator-maintained CBH/Ola (Rtlc) rats were lethally irradiated and reconstituted with spleen and bone marrow cells from fully allogeneic WAG or Wistar (Rtlu) donors. Hematopoietically reconstituted rats were treated with cyclosporine (CsA)4 as prophylaxis for graft-versus-host disease (GVHD) for periods ranging from...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198511000-00002
更新日期:1985-11-01 00:00:00
abstract:BACKGROUND:Although the clinical features of early hepatic artery thrombosis (HAT) are well defined, the features of delayed (more than 4 weeks after transplantation) hepatic artery thrombosis are less clearly defined. The aim of our study was to identify risk factors, clinical presentation, and outcome of management o...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-200106150-00018
更新日期:2001-06-15 00:00:00
abstract:BACKGROUND:Patient-level risk factors for delayed graft function (DGF) have been well described. However, the Organ Procurement and Transplantation Network definition of DGF is based on dialysis in the first week, which is subject to center-level practice patterns. It remains unclear if there are center-level differenc...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0000000000000450
更新日期:2015-05-01 00:00:00
abstract::We reviewed the results of all percutaneous fine needle aspirations (FNA) and open lung biopsies (OLB) after bone marrow transplantation at our center (1984-1987) for the evaluation of focal lung lesions that developed or persisted despite antibiotic administration. We sought to determine the prevalence and types of i...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198908000-00017
更新日期:1989-08-01 00:00:00
abstract:BACKGROUND:DBA/2J kidney allografts, but not heart allografts, are spontaneously accepted indefinitely in C57BL/6 (B6) mice, through regulatory tolerance mechanism dependent on Foxp3 cells. In contrast, B6 kidneys are rejected within a week in DBA/2J recipients. We hypothesized that the tolerogenic difference of the ki...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0000000000002867
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:The role of asymptomatic bacteriuria in kidney transplant recipients is unknown. There is no clear evidence of its effect on transplanted kidney. METHODS:We studied urine cytokines profile among kidney transplant recipients with bacteriuria found in screening examination. Urine cultures were collected in 26...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.tp.0000226072.20185.f8
更新日期:2006-06-27 00:00:00
abstract::If ABO antigens/antibodies play any role in the pathogenesis of acute graft-versus-host disease (GVHD), one would expect the highest incidence of GVHD in recipients of minor ABO-mismatched grafts, followed by ABO-matched grafts, and the lowest incidence in major ABO-mismatched transplants. To test this hypothesis 174 ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198806000-00018
更新日期:1988-06-01 00:00:00
abstract::To determine the extent to which pretransplant immunity resulting from natural infection protects against cytomegalovirus (CMV) disease, we analyzed CMV serology on 153 kidney donor and recipient pairs and followed transplant patients to determine incidence and severity of CMV disease. The overall incidence of CMV dis...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198508000-00010
更新日期:1985-08-01 00:00:00
abstract:BACKGROUND:Co-stimulatory blockade has been shown to prolong allograft survival in different transplant models. We investigated the effect of combining humanized anti-CD80 and anti-CD86 monoclonal antibodies (mAb) with sirolimus in cynomolgus monkey renal transplant recipients. METHODS:After renal transplantation, gro...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.TP.0000066806.10029.7A
更新日期:2003-06-27 00:00:00
abstract::Between December 1983 and August 1985, 110 cadaver transplants were performed at our institution. All were started on cyclosporine (CsA) and prednisone (P) for immunosuppressive therapy. Of the 110 patients, 46 were converted from CsA to azathioprine (AZA) for a variety of reasons (cost, toxicity, patient preference, ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198702000-00012
更新日期:1987-02-01 00:00:00
abstract:BACKGROUND:C-reactive protein (CRP) is a strong predictor of cardiovascular disease, all-cause mortality, and renal allograft loss. Little is known about the effects of immunosuppressive and cardiovascular risk-modifying drugs on CRP in renal transplant recipients. METHODS:We retrospectively identified stable patients...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.tp.0000248864.21574.92
更新日期:2007-01-15 00:00:00
abstract:BACKGROUND:The use of anti-B-cell and T-cell immunosuppressive agents leads to only a few weeks' survival of mouse-to-rat cardiac xenografts. METHODS:BALB/c cardiac xenografts were transplanted to Lewis rats treated with cyclosporine (CsA) and/or cobra venom factor (CVF). RESULTS:CsA alone did not prolong xenograft s...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199805150-00012
更新日期:1998-05-15 00:00:00
abstract:BACKGROUND:Recently, peptides derived from the heavy chain of HLA-B2702 have been shown to modulate immune responses. In this study, we examined the use of these peptides for immunosuppression in a pig to mouse islet xenograft model. METHODS:Purified porcine islets were transplanted in autoimmune (non-obese diabetic) ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199812150-00022
更新日期:1998-12-15 00:00:00
abstract:BACKGROUND:The benefit of conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) in terms of gastrointestinal symptom burden has been evaluated previously using patient-reported outcomes. However, data are lacking concerning the sustained effect of conversion over time, and the pote...
journal_title:Transplantation
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1097/01.tp.0000290678.06523.95
更新日期:2007-12-15 00:00:00
abstract:BACKGROUND:AGI-1096 is a novel phenolic intracellular antioxidant with anti-inflammatory and antiproliferative properties. In vitro, AGI-1096 inhibited the inducible expression of vascular cell adhesion molecule (VCAM)-1, E-selectin, and monocyte chemoattractant protein (MCP)-1 in endothelial cells and tumor necrosis f...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.tp.0000123076.05313.9f
更新日期:2004-05-27 00:00:00
abstract::Enhancement of skin grafts in mice by passively administered alloantiserum was examined in conjunction with the simultaneous use of other immunosuppressive regimens. It could be clearly shown that when a "weak" antilymphocyte serum (ALS) was used, a significant further prolongation of graft survival occurred over that...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-197509000-00009
更新日期:1975-09-01 00:00:00
abstract:BACKGROUND:Altered expression of murine MD-1, a molecule controlling expression of members of the interleukin (IL)-1 receptor family of signaling proteins, regulates antigen-presenting cell-induced alloreactions. We investigated the effect of treatment with antisense deoxyoligonucleotides or antibodies to MD-1 in vivo ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-200206150-00013
更新日期:2002-06-15 00:00:00
abstract:BACKGROUND:To reduce the morbidity of living kidney donors we introduced ketorolac-based analgesia for patients undergoing open donor nephrectomy in August 1999. There are no prior reports on the use of ketorolac for patients undergoing donor nephrectomy. METHODS:We conducted a retrospective review of all 198 consecut...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-200203150-00014
更新日期:2002-03-15 00:00:00
abstract::The effect of the tritiated thymidine (3H-TdR) suicide technique on the ability of donor cells to induce fatal graft-versus-host disease (GVHD) was studied. C57BL/6 (H-2b) spleen cells were stimulated in vitro with irradiated BALB/c (H-2d) Moloney lymphoma cells in mixed culture and 3H-TdR of high-specific activity ad...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-197704000-00001
更新日期:1977-04-01 00:00:00
abstract::Patients awaiting a renal transplant were given 1 HLA-DR antigen-matched blood in order to compare the sensitization and graft outcome of these patients with those of control patients, who had been given random blood before transplantation. No differences in sensitization, measured by the formation of HLA antibodies, ...
journal_title:Transplantation
pub_type: 临床试验,杂志文章
doi:
更新日期:1994-10-15 00:00:00
abstract::Despite great improvements in renal allograft survival over the last 3 decades, long-term graft loss, particularly through antibody-mediated rejection, remains the bane of kidney transplantation. Interindividual patient variation means that a given immunosuppressive regimen may be inadequate in certain patients and ex...
journal_title:Transplantation
pub_type: 杂志文章,评审
doi:10.1097/TP.0b013e3181a2e295
更新日期:2009-05-15 00:00:00
abstract:BACKGROUND:Kidneys from infectious risk donors (IRD) confer substantial survival benefit in adults, yet the benefit of IRD kidneys to pediatric candidates remains unclear in the context of high waitlist prioritization. METHODS:Using 2010-2016 Scientific Registry of Transplant Recipients data, we studied 2417 pediatric...
journal_title:Transplantation
pub_type: 杂志文章,多中心研究
doi:10.1097/TP.0000000000002674
更新日期:2019-12-01 00:00:00
abstract::The effect of cyclosporine on lymphocyte intracellular free calcium [( Ca2+]i) is controversial, and potential age-related differences in lymphocyte CsA sensitivity have not been studied. We measured the mitogen-induced change in [Ca2+]i in peripheral blood lymphocytes (PBLs) following intravenous CsA infusion (5 mg/k...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199108000-00031
更新日期:1991-08-01 00:00:00
abstract:BACKGROUND:Acute liver failure (ALF) carries a high mortality unless urgent orthotopic liver transplantation (OLT) is performed on time. Live donors are utilized to treat this irreversible condition first in pediatric cases and then in adults. Herein, we aimed to report our experience with live donors for ALF in a coun...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.tp.0000276987.55382.e2
更新日期:2007-08-27 00:00:00