Alteration in CD45RBhi/CD45RBlo T-cell ratio following CD45RB monoclonal-antibody therapy occurs by selective deletion of CD45RBhi effector cells.

Abstract:

:Tolerance induction by CD45RB monoclonal antibody (mAb) in murine allograft models is associated with an alteration in the CD45RBlo/CD45RBhi T-cell ratio in favor of CD45RBlo T cells, which can function as regulatory cells and promote tolerance. It has been proposed that inversion of the CD45RBhi/CD45RBlo normal T-cell ratio by mAb can occur by down-regulation of CD45RB surface molecules expressed by T cells. Because CD45RB mAb infusion can lead to a reduction in peripheral T cells, we tested whether other mechanisms might participate in the inversion of the CD45RBhi/CD45RBlo ratio, including apoptosis of CD45RBhi cells. We report that CD45RB mAb led to rapid elimination of both CD4+ and CD8+ T cells in vitro. Importantly, CD45RB mAb selectively eliminated CD45RBhi T cells without affecting the viability of CD45RBlo T cells. Furthermore, the death of T cells occurred with a reduction in mitochondrial transmembrane potential and DNA fragmentation but with little evidence of nuclear condensation and cell shrinkage typically found with cells undergoing apoptosis. We propose that CD45RB mAb therapy may promote a dominant regulatory T-cell population that has the capacity to inhibit rejection by the selective elimination of CD45RBhi effector T cells. This occurs by a process that does not involve the classic morphologic features of apoptosis. Strategies that facilitate an inversion of the CD45RBhi/CD45RBlo T-cell subset ratio may improve the efficacy of CD45RB mAb, and therapeutic measures that prevent deletion of CD45RBhi T cells may need to be avoided to achieve tolerance clinically.

journal_name

Transplantation

journal_title

Transplantation

authors

Luke PP,Deng JP,O'Brien CA,Everest M,Hall AV,Chakrabarti S,O'Connell PJ,Zhong R,Jevnikar AM

doi

10.1097/01.TP.0000072373.77323.D4

subject

Has Abstract

pub_date

2003-07-27 00:00:00

pages

400-9

issue

2

eissn

0041-1337

issn

1534-6080

journal_volume

76

pub_type

杂志文章
  • Impact of simultaneous pancreas and kidney transplantation on cardiovascular risk factors in patients with type 1 diabetes mellitus.

    abstract::We retrospectively investigated the impact of pancreas transplantation on cardiovascular disease risk factors in patients with type 1 diabetic end-stage renal disease (ESRD). Two cohorts of patients, 44 simultaneous pancreas and kidney transplant patients (SPK) and 30 kidney transplant-alone patients (KTA), were inclu...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/01.tp.0000270617.43811.af

    authors: Luan FL,Miles CD,Cibrik DM,Ojo AO

    更新日期:2007-08-27 00:00:00

  • Successful liver transplantation of two brothers with crigler-najjar syndrome type 1 using a single cadaveric organ.

    abstract::Crigler-Najjar type 1 disease (CNS1) is the result of a genetic defect, leading to complete functional loss of an enzyme which glucuronidates bilirubin. As a consequence, unconjugated bilirubin accumulates and may cause kernicterus, the most serious complication in adolescents. Phototherapy effectively adjusts bilirub...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-200201150-00012

    authors: Schauer R,Lang T,Zimmermann A,Stangl M,Da Silva L,Schildberg FW,Rau HG

    更新日期:2002-01-15 00:00:00

  • Renal function after kidney transplantation in children. A comparison of conventional immunosuppression with cyclosporine.

    abstract::Clearance studies were performed in 32 transplanted children treated with CsA in combination with low-dose prednisolone (CsA group), and the results were compared with those of 29 children transplanted earlier and treated with azathioprine and prednisolone (CIS group). Serum creatinine and urea levels 6 weeks and 1 ye...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-198704000-00006

    authors: Hoyer PF,Krohn HP,Offner G,Byrd DJ,Brodehl J,Wonigeit K,Pichlmayr R

    更新日期:1987-04-01 00:00:00

  • Conversion from cyclosporine to azathioprine in renal allograft recipients.

    abstract::Fifty seven recipients of renal allografts initially treated with CsA and low-dose prednisone were switched to azathioprine and low-dose steroids. Ten had prolonged (greater than 28 days) allograft nonfunction after transplantation (group 1), 8 had ongoing, poorly controlled rejection (group 2), and 39 had stable func...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-198412000-00024

    authors: Rocher LL,Milford EL,Kirkman RL,Carpenter CB,Strom TB,Tilney NL

    更新日期:1984-12-01 00:00:00

  • Failure to alter neonatal transplantation tolerance by the injection of interleukin 2.

    abstract::It has been postulated that the establishment of acquired, neonatal immunologic tolerance is due to a "deficit" in interleukin 2 (IL-2). To test this hypothesis, chickens were made immunologically tolerant to both major and minor histocompatibility antigens by transplantation of skin grafts onto newly hatched recipien...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-198802000-00041

    authors: Tempelis CH,Hála K,Krömer G,Schauenstein K,Wick G

    更新日期:1988-02-01 00:00:00

  • Alterations in rat pulmonary macrophage function by the immunosuppressive agents cyclosporine, azathioprine, and prednisolone.

    abstract::Disturbances of the immune response of the lung induced by the action of immunosuppressive agents on the functional abilities of rat pulmonary alveolar macrophages (PAM) were analyzed following in vitro incubation or in vivo administration (for 30 days) of cyclosporinea, (CsA) azathioprine (Az) or prednisolone (Pr). T...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-198306000-00014

    authors: Drath DB,Kahan BD

    更新日期:1983-06-01 00:00:00

  • Association of cytomegalovirus genotype with graft rejection after liver transplantation.

    abstract:BACKGROUND:The envelope glycoprotein gB of human cytomegalovirus (CMV) occurs as one of four main genotypes. Some previous studies have proposed a relationship of CMV gB genotype to the frequency of symptomatic infection and to clinical outcomes in both transplant and human immunodeficiency virus-infected populations. ...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199812270-00010

    authors: Rosen HR,Corless CL,Rabkin J,Chou S

    更新日期:1998-12-27 00:00:00

  • Thymoglobulin induction decreases rejection in solitary pancreas transplantation.

    abstract:BACKGROUND:Solitary pancreas transplants, both pancreas transplant alone (PTA) and pancreas after kidney (PAK), have higher rejection rates and lower graft survivals than simultaneous pancreas-kidney transplants (SPK). The aim of this study is to compare three different antibody induction regimens in solitary pancreas ...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-200111270-00017

    authors: Stegall MD,Kim DY,Prieto M,Cohen AJ,Griffin MD,Schwab TR,Nyberg SL,Velosa JA,Gloor JM,Innocenti F,Bohorquez H,Dean PG,Carpenter HA,Leontovich ON,Sterioff S,Larson TS

    更新日期:2001-11-27 00:00:00

  • Acquired systemic tolerance to rat cardiac allografts induced by intrathymic inoculation of synthetic polymorphic MHC class I allopeptides.

    abstract::This study extends the finding that intrathymic (IT) injection of 3M KC1 extracts of T cells induces transplant tolerance to the use of well defined polymorphic MHC class I allopeptides derived from the hypervariable domain of RT1.Au (WF MHC class I). While three of the six synthetic RT1.Au peptides were immunogenic, ...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199612270-00034

    authors: Chowdhury NC,Murphy B,Sayegh MH,Jin MX,Roy DK,Hardy MA,Oluwole SF

    更新日期:1996-12-27 00:00:00

  • Dietary omega-3 and omega-9 fatty acids uniquely enhance allograft survival in cyclosporine-treated and donor-specific transfusion-treated rats.

    abstract:BACKGROUND:Both laboratory and clinical studies have shown that dietary lipids may affect immunologic responses. This study was conducted to compare different classes of long-chain unsaturated fatty acids for their effect on allograft survival in animals receiving a donor-specific transfusion and a short course of low-...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199805270-00004

    authors: Alexander JW,Valente JF,Greenberg NA,Custer DA,Ogle CK,Gibson SW,Babcock GF

    更新日期:1998-05-27 00:00:00

  • Alloreactive cytotoxic T lymphocytes focus on specific major histocompatibility complex-bound peptides.

    abstract::Alloreactive T cells are often specific for individual peptides that are bound to allogeneic major histocompatibility complex (MHC) molecules. Other alloreactive T cells are reported to be peptide-independent or to recognize MHC conformational changes that are induced by multiple peptides. We tested 12 anti-HLA-B7 all...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199707270-00030

    authors: Smith KD,Huczko E,Engelhard VH,Li YY,Lutz CT

    更新日期:1997-07-27 00:00:00

  • Renal xenografts from triple-transgenic pigs are not hyperacutely rejected but cause coagulopathy in non-immunosuppressed baboons.

    abstract:BACKGROUND:The genetic modification of pigs is a powerful strategy that may ultimately enable successful xenotransplantation of porcine organs into humans. METHODS:Transgenic pigs were produced by microinjection of gene constructs for human complement regulatory proteins CD55 and CD59 and the enzyme alpha1,2-fucosyltr...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-200006270-00008

    authors: Cowan PJ,Aminian A,Barlow H,Brown AA,Chen CG,Fisicaro N,Francis DM,Goodman DJ,Han W,Kurek M,Nottle MB,Pearse MJ,Salvaris E,Shinkel TA,Stainsby GV,Stewart AB,d'Apice AJ

    更新日期:2000-06-27 00:00:00

  • Copeptin, a surrogate marker of vasopressin, is associated with accelerated renal function decline in renal transplant recipients.

    abstract:BACKGROUND:Chronically elevated vasopressin (VP) plasma levels have been shown to induce accelerated renal function decline in rats with chronic renal failure. Whether endogenous VP is a renal risk factor in humans has not been investigated yet. We aimed to investigate whether, in renal transplant recipients, VP concen...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0b013e3181b11ae4

    authors: Meijer E,Bakker SJ,de Jong PE,Homan van der Heide JJ,van Son WJ,Struck J,Lems SP,Gansevoort RT

    更新日期:2009-08-27 00:00:00

  • Delayed correction of portal hypertension after portal vein conduit arterialization in liver transplantation.

    abstract::A 55-year-old woman underwent orthotopic liver transplantation for autoimmune chronic active hepatitis. Extensive portal and superior mesenteric venous thrombosis precluded standard portal venous reconstruction and necessitated use of a venous conduit from the recipient splenic vein of the donor liver. Flow through th...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199704150-00022

    authors: Neelamekam TK,Geoghegan JG,Curry M,Hegarty JE,Traynor O,McEntee GP

    更新日期:1997-04-15 00:00:00

  • Late onset of severe graft-versus-host disease in a pediatric liver transplant recipient.

    abstract::We report the management of a patient with the late onset of chronic graft-versus-host disease (GVHD) after orthotopic liver transplantation. GVHD is a rare complication of solid organ transplants that usually presents early after transplantation and is fatal in the majority of cases. Our patient differs from the typi...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-200105270-00022

    authors: Dunn SP,Krueger LJ,Butani L,Punnett H

    更新日期:2001-05-27 00:00:00

  • Cytomegalovirus PP65 antigenemia monitoring as a guide for preemptive therapy: a cost effective strategy for prevention of cytomegalovirus disease in adult liver transplant recipients.

    abstract:BACKGROUND:The aim of the study was to assess the incidence of cytomegalovirus (CMV) infection and disease in adult liver transplant recipients, using routine preemptive therapy guided by the pp65 antigenemia test. METHODS:Antigenemia was monitored weekly after liver transplantation (OLTX) for the first 3 months, and ...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199910270-00011

    authors: Kusne S,Grossi P,Irish W,St George K,Rinaldo C,Rakela J,Fung J

    更新日期:1999-10-27 00:00:00

  • A computerized system for the selection of organ transplant recipients.

    abstract::The Southeastern Regional Organ Procurement Program has developed a computerized system for the selection of organ transplant recipients. This system has proven to be a useful method for the rapid selection of histocompatible recipients for organ transplants from a large pool of potential recipients in a wide geograp...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-197501000-00005

    authors: Stulting RD,Ward FE

    更新日期:1975-01-01 00:00:00

  • Liver transplantation for alcoholic cirrhosis: long term follow-up and impact of disease recurrence.

    abstract:BACKGROUND:Alcoholic liver disease has emerged as a leading indication for hepatic transplantation, although it is a controversial use of resources. We aimed to examine all aspects of liver transplantation associated with alcohol abuse. METHODS:Retrospective cohort analysis of 123 alcoholic patients with a median of 7...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-200108270-00010

    authors: Bellamy CO,DiMartini AM,Ruppert K,Jain A,Dodson F,Torbenson M,Starzl TE,Fung JJ,Demetris AJ

    更新日期:2001-08-27 00:00:00

  • Clinical and laboratory evaluation of the safety of a bioartificial liver assist device for potential transmission of porcine endogenous retrovirus.

    abstract:BACKGROUND:The potential risk of transmission of porcine endogenous retroviruses (PERV) from xenogeneic donors into humans has been widely debated. Because we were involved in a phase I/II clinical trial using a bioartificial liver support system (BLSS), we proceeded to evaluate the biosafety of this device. MATERIALS...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-200202150-00017

    authors: Kuddus R,Patzer JF 2nd,Lopez R,Mazariegos GV,Meighen B,Kramer DJ,Rao AS

    更新日期:2002-02-15 00:00:00

  • Pretransplant low CD3+CD25high cell counts or a low CD3+CD25high/CD3+HLA-DR+ ratio are associated with an increased risk to acute renal allograft rejection.

    abstract:BACKGROUND:Detection of markers predicting allograft rejection is important for risk assessment before kidney transplantation, as well as to minimize posttransplantation immunosuppression. METHODS:We studied the expression of CD25, HLA-DR, CD134, CD62L, and CD44 by flow cytometry in CD4, CD8, and CD3 cells, from pretr...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0b013e3182283c58

    authors: Hueso M,Mestre M,Benavente Y,Bas J,Grinyó JM,Navarro E

    更新日期:2011-09-15 00:00:00

  • Rapamycin Prolongs Graft Survival and Induces CD4+IFN-γ+IL-10+ Regulatory Type 1 Cells in Old Recipient Mice.

    abstract:BACKGROUND:Although the elderly represents a rapidly growing population among transplant recipients, age-specific aspects have not been considered sufficiently in clinical trials. Moreover, age-specific effects of immunosuppressive therapies remain poorly understood. METHODS:Here, we assessed the impact of rapamycin o...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0000000000001902

    authors: Quante M,Heinbokel T,Edtinger K,Minami K,Uehara H,Nian Y,Azuma H,Abdi R,Elkhal A,Tullius SG

    更新日期:2018-01-01 00:00:00

  • Constitutive activation of Jak/STAT proteins in Epstein-Barr virus-infected B-cell lines from patients with posttransplant lymphoproliferative disorder.

    abstract:BACKGROUND:Posttransplant lymphoproliferative disease (PTLD) is a major complication after bone marrow and solid organ transplantation. The disease encompasses a spectrum of abnormal, Epstein-Barr virus (EBV)-associated B-cell proliferations. We have previously shown that EBV-infected, spontaneous lymphoblastoid cell l...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-200208150-00017

    authors: Nepomuceno RR,Snow AL,Robert Beatty P,Krams SM,Martinez OM

    更新日期:2002-08-15 00:00:00

  • Results of a prospective randomized trial of sirolimus conversion in kidney transplant recipients on early corticosteroid withdrawal.

    abstract:BACKGROUND:The use of calcineurin inhibitors is associated with chronic nephrotoxicity and lower glomerular filtration rate (GFR). As a result, one strategy of transplant immunosuppression is calcineurin inhibitor elimination. METHODS:The aim of this study was to determine the outcome of a prospective randomized trial...

    journal_title:Transplantation

    pub_type: 杂志文章,随机对照试验

    doi:10.1097/TP.0b013e31822805d7

    authors: Heilman RL,Younan K,Wadei HM,Mai ML,Reddy KS,Chakkera HA,Gonwa TA

    更新日期:2011-10-15 00:00:00

  • Reduced human IgG anti-ATGAM antibody formation in renal transplant recipients receiving mycophenolate mofetil.

    abstract::Exposure to the equine-derived polyclonal antithymocyte preparation, ATGAM, frequently elicits human anti-ATGAM antibody formation. The influence of concomitant immunosuppressants on this antiantibody response has not been established. We therefore evaluated IgG antibody formation to ATGAM in 47 patients receiving ATG...

    journal_title:Transplantation

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/00007890-199560120-00001

    authors: Kimball JA,Pescovitz MD,Book BK,Norman DJ

    更新日期:1995-12-27 00:00:00

  • Posttransplant bone disease: a case illustrating dramatic improvements in bone density with vitamin D replacement therapy.

    abstract::Although bisphosponates are proposed as first-line treatment for posttransplant bone disease they are not optimal in all situations. A kidney transplant recipient developed hypercalcemia from mobilization of extraskeletal calcium. He had low serum parathyroid hormone and vitamin D; high calcium excretion; and normal c...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-200106270-00025

    authors: Dhingra RK,Sprague SM,Ojo AO,Leavey SF

    更新日期:2001-06-27 00:00:00

  • Double renal transplant from infant donors. A good alternative for adult recipients.

    abstract::Several groups have reported technical complications and poor graft survival rates in kidney transplants from pediatric donors to adult recipients. Increased incidences of acute rejections, vascular thrombosis, and early glomerulosclerotic lesions have led many groups to abandon this graft combination. Over the last 4...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199601150-00009

    authors: Portolés J,Marañes A,Prats D,Torrente J,Marrón B,Perez-Contín MJ,Herrero JA,Coronel F,Grimalt J,Barrientos A

    更新日期:1996-01-15 00:00:00

  • Long-term benefits of mycophenolate mofetil after heart transplantation.

    abstract::Transplant coronary artery disease and malignancy are the major limitations to survival after heart transplantation. In a randomized trial, mycophenolate mofetil (MMF) significantly improved 3-year survival over azathioprine, but the expected reduction in intracoronary ultrasound evidence of vasculopathy was not found...

    journal_title:Transplantation

    pub_type: 杂志文章,评审

    doi:10.1097/01.tp.0000153302.27299.16

    authors: Keogh A

    更新日期:2005-02-15 00:00:00

  • Urine cytokines profile in renal transplant patients with asymptomatic bacteriuria.

    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

    authors: Ciszek M,Paczek L,Bartłomiejczyk I,Mucha K

    更新日期:2006-06-27 00:00:00

  • Polyclonal rabbit gamma globulins against a human cytotoxic CD4+ T cell clone. I. Clone characteristics and antiblast globulin preparation.

    abstract::Antihuman lymphocyte rabbit (or horse) gamma globulins used in recipients of organ transplantation are prepared against thymocytes or immortalized cell lines, the only two sources so far allowing enough antigen preparation. These cells lack, however, the surface determinants characteristic of alloreactive blasts invol...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-198908000-00014

    authors: Bonneville M,Carcagne J,Vie H,Moreau JF,Chevalier S,Latour M,Carosella E,Soulillou JP

    更新日期:1989-08-01 00:00:00

  • Apolipoprotein E gene polymorphism alters lipids before pancreas transplantation.

    abstract:BACKGROUND:Pancreas transplantation (PTX) improves lipids in patients with type 1 diabetes mellitus. However, there are patients who have persistent abnormal lipids or develop new hyperlipidemia despite PTX. One factor that may influence the lipid profile is apolipoprotein E (Apo E) genotype. Apo E polymorphism, partic...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-200210150-00013

    authors: Balakrishnan S,Colling C,Burkman T,Erickson J,Lyden E,Maheshwari H,Mack-Shipman L,Lane J,Larsen J

    更新日期:2002-10-15 00:00:00