Abstract:
OBJECTIVE:The immunomodulator, FTY720, lowers the peripheral lymphocyte count (PLC) by inducing migration of circulating lymphocytes to secondary lymphoid organs. We investigated the efficacy of mono- vs. combined-FTY720/CsA therapy on graft survival (GS) and on lowering the PLC in a solid organ and a skin graft model, using strains with strong MHC disparity. METHODS:Heterotopic cardiac or tail skin grafting was performed using the DA (RT1a) to Lewis (RT1(1)) rat strain combination. FTY720 was administered as a single daily dose by gavage alone or in combination with subcutaneously delivered CsA. PLC, body weight and drug concentrations were determined on day 7, 28, or the day of rejection. MAIN FINDINGS:In placebo-treated animals the heart and skin allografts rejected after 6 and 8 days. FTY720 delayed rejection of both the solid organ and skin grafts. The maximal effect was achieved at 1 mg x kg(-l) x day(-1) FTY720, resulting in a median survival time (MST) of 14 days for both allotransplants comparable to the effect achieved by 1 mg x kg x day(-1) CsA in both models. In the cardiac graft experiment with CsA co-administration, doses of 0.3 and 1 mg/kg were used. Under these conditions very small doses of FTY720 were effective in maintaining grafts throughout the treatment period. Adding higher FTY720 doses to the 1 mg x kg(-1) x day(-1) CsA was needed to effectively extend the skin GS, e.g. 0.3 mg x kg(-l) x day(-1) FTY720 prolonged GS from 13 to 47.5 days MST, i.e. well beyond the 28 day-treatment period. CsA did not influence the PLC at clinically relevant doses. FTY720 lowered the PLC significantly and dose-dependently, at doses lower than those needed for the prolongation of both cardiac and skin GS with FTY720 monotherapy. In rats with skin grafts the PLC was markedly lowered up to 1 mg x kg(-1) x day(-1) FTY720, whereas, in the heart model, it was lowered up to 0.1 mg x kg(-1) x day(-1). Independently of the graft type, within the combination regimens 0.3 mg x kg(-1) x day(-1) FTY720 achieved a maximal PLC depletion. CONCLUSIONS:Combining FTY720 and CsA was very well tolerated with respect to weight gain and lack of any clinically detectable infections. In the strain combination used FTY720 monotherapy was less effective than previously reported in maintaining grafts. The two-drug regimens extended strikingly the GS for both models. However, the prolongation of the heart GS was smoothly dose-related with FTY720 doses ranging from 0.01 to 1 mg x kg(-1) x day(-1) , whereas, the skin graft prolongation was modest at doses up to 0.1 mg x kg(-1) x day(-1) and remarkably enhanced at 0.3 and 1 mg x kg(-1) x day(-1) FTY720.
journal_name
Transpl Immunoljournal_title
Transplant immunologyauthors
Nikolova Z,Hof A,Baumlin Y,Hof RPdoi
10.1016/s0966-3274(01)00031-4subject
Has Abstractpub_date
2001-02-01 00:00:00pages
267-77issue
4eissn
0966-3274issn
1878-5492pii
S0966327401000314journal_volume
8pub_type
杂志文章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::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::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::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: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::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::Although immunosuppressive therapies have made organ transplantation a common medical procedure worldwide, chronic toxicity is a major issue of long-term treatment. One method to improve such therapies is the application of immunomodulatory agents from parasites, such as Hypoderma lineatum (Diptera: Oestridae). Hypode...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2018.09.001
更新日期:2018-12-01 00:00:00
abstract::CD4(+)CD25(high) T cells named regulatory T (Treg) cells are generated and play a key role in the induction and maintenance of transplant tolerance in organ recipients. Interleukin-2 (IL-2) enhance the development of effector cells and is essential for generation of Treg cells. The effect of the anti-CD25 monoclonal a...
journal_title:Transplant immunology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.trim.2008.01.005
更新日期:2008-04-01 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::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:BACKGROUND:The importance of apoptosis contra necrosis for ischemia/reperfusion (RP) and acute rejection in concordant rodent xenotransplantation is largely unknown. We explored this question by comparing rodent allo and concordant xenotransplants with different morphological methods to detect apoptosis and biochemical...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/S0966-3274(03)00018-2
更新日期:2003-10-01 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: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::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::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::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::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::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: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::The neomacrolide antibiotic azithromycin is known to have an anti-inflammatory effect and is increasingly being used in the treatment of chronic inflammatory pulmonary diseases. We investigated whether azithromycin influenced matrix remodeling. Matrix metalloproteinase (MMP)-9 protein levels were measured by ELISA in ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2011.06.006
更新日期:2011-09-01 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: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:BACKGROUND:Blockade of costimulation signaling required for immune response, such as CD40/CD40L and CD28/B7, is a reasonable strategy to prevent rejection and in defined combinations may allow donor specific tolerance. Indeed, in rodents, costimulation blockade with CD28/B7 antagonists or with CD40Ig was able to induce...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2012.10.004
更新日期:2012-12-01 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: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::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: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::Desferrioxamine (DFO), commonly used in therapy as a chelator of ferric ion in disorders of iron overload, is a potent inhibitor of human cytomegalovirus (HCMV) replication in cultured fibroblast cells. Moreover, DFO has immunomodulatory activity both in vitro and in vivo. We studied DFO effects on HCMV replication in...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/0966-3274(95)80017-4
更新日期:1995-12-01 00:00:00
abstract:BACKGROUND:Ischemia reperfusion injury (IRI) is one of the risk factors for delayed graft function, acute rejection and long term allograft survival after kidney transplantation. IRI is an independent antigen inflammatory process that produces tissue damage. Our objective was to study the impact of immunosuppressive tr...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2010.10.006
更新日期:2011-01-15 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