Abstract:
BACKGROUND:Many models of transplant tolerance have been found to depend on the induction of regulatory T cells (Tregs). Innate immune signals are known to suppress Tregs thereby augmenting immunity by abrogating Treg function. Such signals may also provide a barrier to transplantation tolerance mediated by Tregs. A number of cell surface molecules expressed by Tregs have been found to inhibit Treg activity, the best characterized of which is the glucocorticoid-induced tumor necrosis factor receptor-related (GITR) protein. METHODS:By using an adoptive transfer model of allograft rejection, we can study the effects of inflammation and antigen-specific Tregs on graft survival. Inflammation resulting from the transplant procedure counter-regulates the suppressor activity of Tregs. To assess whether Treg activity could be enhanced by blocking GITR signaling, we compared the capacity of Tregs to prolong the survival of grafts in the presence or absence of activation-inducible TNF receptor (AITRL)-Fc, a novel construct that binds GITR. RESULTS:We report that interruption of GITR-GITR ligand (GITRL) binding by AITRL-Fc resulted in long-term Treg-dependent acceptance of skin grafts in the setting of innate immune signals that otherwise interfere with Treg activity. CONCLUSIONS:Inflammation and other innate immune signals may activate antigen presenting cells to upregulate GITRL. GITR-GITRL interaction is one pathway by which antigen presenting cells may enhance the adaptive response to foreign antigen by counter-regulating Tregs and by costimulating effector T cells. By blocking this interaction with AITRL-Fc, one can sustain the benefit conferred by graft-protective Tregs.
journal_name
Transplantationjournal_title
Transplantationauthors
Sonawane SB,Kim JI,Lee MK,Lee SH,Duff PE,Moore DJ,Lian MM,Deng S,Choi Y,Yeh H,Caton AJ,Markmann JFdoi
10.1097/TP.0b013e3181ba6f85subject
Has Abstractpub_date
2009-11-27 00:00:00pages
1169-77issue
10eissn
0041-1337issn
1534-6080pii
00007890-200911270-00005journal_volume
88pub_type
杂志文章相关文献
TRANSPLANTATION文献大全abstract:BACKGROUND:The chemokine receptor CCR7 plays a pivotal role in the homing of naïve T cells and regulatory T cells to secondary lymphoid organs and the migration of dendritic cells into afferent lymphatic vessels. Antigen presentation, T cell recruitment, and expansion of regulatory cells are crucial events in establish...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0b013e3181826a97
更新日期:2008-08-27 00:00:00
abstract:BACKGROUND:Many recipients of lung transplants from brain-dead donors develop bronchiolitis obliterans, a manifestation of chronic rejection. It has been shown that brain death increases inflammatory mediators and accelerates acute rejection in kidney, liver, and heart transplants. In this study, the authors investigat...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.tp.0000142679.45418.96
更新日期:2004-11-15 00:00:00
abstract:BACKGROUND:Graft coronary artery disease (CAD) is an increasingly important problem during long-term survival after heart transplantation, but the importance of cellular rejection, in particular late after transplantation, remains undetermined. METHODS AND RESULTS:We analyzed 492 coronary angiographies (967+/-705 days...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199802270-00015
更新日期:1998-02-27 00:00:00
abstract:BACKGROUND:Allogeneic bone marrow transplantation (BMT) and donor lymphocyte infusion (DLI) provide valuable treatments for a range of diseases. However, the therapeutic utility of BMT and DLI is reduced by the high incidence of graft-versus-host disease (GvHD) mediated by activated donor T lymphocytes directed against...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.tp.0000229435.58898.c5
更新日期:2006-08-27 00:00:00
abstract::In this report we describe a modified, sensitive MLR test that appears to detect fine antigenic disparities between HLA-identical siblings confirmed as such by serology and the standard MLR test. In a group of 40 consecutive allogeneic bone marrow transplants, reactivity detected by the modified MLR test correlated wi...
journal_title:Transplantation
pub_type: 杂志文章
doi:
更新日期:1994-05-27 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:Ischemia-reperfusion (I/R) injury after lung transplantation causes alveolar damage, lung edema, and acute rejection. Poly(adenosine diphosphate-ribose) polymerase (PARP) is a single-stranded DNA repair enzyme that induces apoptosis and necrosis after DNA damage caused by reactive oxygen species. We evaluate...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0000000000000305
更新日期:2014-09-27 00:00:00
abstract::Hepatitis C viral recurrence after orthotopic liver transplantation is almost universal. Hepatitis C induced graft failure may occur, but the clinical and histologic profiles are not well defined. The aim of this study was to describe the pattern of early graft failure in patients with recurrent hepatitis C after live...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199603150-00005
更新日期:1996-03-15 00:00:00
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
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:The inflammatory reaction that occurs during the 5 days after transplantation led at 3 days to the death of 70% of injected myoblasts. Use of anti-inflammatory agents appeared to be a possible way to increase myoblast survival. The application of gene transfer techniques to cell transplantation offers the po...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199803270-00005
更新日期:1998-03-27 00:00:00
abstract:BACKGROUND:Human herpesvirus-6 (HHV-6) is known to reactivate after renal transplantation and has been associated with several clinical manifestations. Risk factors for sustained viral replication, however, remain unclear. METHODS:Thirty consecutive kidney transplant patients were prospectively followed for HHV-6 repl...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0b013e3182807ab7
更新日期:2013-03-27 00:00:00
abstract::The nephrotoxic effects of cyclosporine (CsA) seem to be augmented by co-existing renal injury. A high rate of prolonged delayed function (acute tubular necrosis [ATN]) and non-function (NF) has been associated with the use of CsA prior to and following renal transplantation. Cyclosporine has also been associated with...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198701000-00019
更新日期:1987-01-01 00:00:00
abstract:BACKGROUND:Host macrophages are abundant within fetal pig pancreas xenografts undergoing rejection, but their role is unknown. Therefore, we examined the effect of host macrophage depletion on xenograft rejection. METHODS:Nonobese diabetic (NOD) mice were given clodronate-loaded liposomes intravenously to deplete macr...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199812150-00002
更新日期:1998-12-15 00:00:00
abstract:BACKGROUND:Rat lung allograft rejection is mediated by collagen type V (col(V)) specific T-helper-cell 17 (Th17) cells. Adoptive transfer of these cells is sufficient to induce rejection pathology in isografts, whereas tolerance to col(V) suppresses allograft rejection. Therefore, we tested whether regulatory T cells f...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0b013e3181bcde7b
更新日期:2009-12-27 00:00:00
abstract::Unstimulated whole saliva and serum samples were collected from ten allogeneic bone marrow transplant recipients before and after bone marrow transplantation, seven donors, and from twenty healthy individuals. Two patterns with regard to salivary IgA were found after transplantation. In five patients, a short-lasting ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198811000-00016
更新日期:1988-11-01 00:00:00
abstract:BACKGROUND:Currently, the severity of veno-occlusive disease (VOD) is graded retrospectively on the basis of the evolution of clinical and biological criteria. The objective of this study was to describe a noninvasive method capable of predicting the severity of this disease at the time of the diagnosis. METHODS:Seven...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-200207150-00011
更新日期:2002-07-15 00:00:00
abstract::Preventing hyperacute rejection (HAR) is a difficult and unsolved problem in xenotransplantation. This may be due, in part, to a lack of therapies that can suppress production of natural antibodies (NA), which are thought to be critical mediators of HAR. This study examined the effect of 15-deoxyspergualin (DSPG) and ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199207000-00004
更新日期:1992-07-01 00:00:00
abstract::We have investigated the influence of phenobarbitone ([PB]; 40 mg/kg/day), an inducer of hepatic drug metabolism, on high-dose cyclosporine ([CsA] 40 mg/kg/day) nephrotoxicity in normal Lewis (Lew) and renal allografted (DA X Lew F1----Lew) rats of both sexes. In untreated normal animals, CsA nephrotoxicity, assessed ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198804000-00005
更新日期:1988-04-01 00:00:00
abstract::When normal mice are exposed for short periods to ultraviolet light (UV), they support the progressive growth of transplanted syngeneic UV-induced tumors. Normal nonirradiated mice almost always reject these tumor implants. The UV-mediated suppression of the antitumor response can be adoptively transferred to normal s...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-197708000-00005
更新日期:1977-08-01 00:00:00
abstract:BACKGROUND:Immunosuppression in renal transplantation, although manageable in the short-term, is a major hurdle for long-term graft survival. Recently, increased frequencies of CD4CD25 regulatory T cells (Tregs) have been described as an additional mechanism that induces alloimmune tolerance. METHODS:We assessed 64 re...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.tp.0000229473.95202.50
更新日期:2006-08-27 00:00:00
abstract:BACKGROUND:Heart transplantation (HTx) remains the most effective long-term treatment for advanced heart failure. Primary graft dysfunction (PGD) continues to be a potentially life-threatening early complication. In 2014, a consensus statement released by International Society for Heart and Lung Transplantation (ISHLT)...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0000000000002220
更新日期:2019-02-01 00:00:00
abstract:BACKGROUND:Antibody-mediated rejection (AMR) remains associated with reduced kidney graft survival and no clear prognostic marker is available. METHODS:We investigated whether donor-specific antibodies (DSA) ability to bind C1q in comparison with AMR C4d status, both indirect signs of complement activation, improve ri...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0000000000002265
更新日期:2018-11-01 00:00:00
abstract:BACKGROUND:Brain death (BD) affects the viability of lungs for transplantation. A correlation exists between high lung inflammation after BD and the decrease in female sex hormones, especially estradiol. Therefore, we investigated the effects of 17β-estradiol (E2) treatment on the lungs of female brain dead rats. METH...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0000000000003467
更新日期:2020-10-07 00:00:00
abstract:BACKGROUND:Preoperative mapping of the hepatic venous system of the partial liver graft is indispensable to the success of living-related liver transplantation. We assessed the accuracy of magnetic resonance (MR) venography with angular reconstruction in depicting the tributaries of the middle hepatic vein and left hep...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199907270-00019
更新日期:1999-07-27 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:BACKGROUND:Tacrolimus is a potent immunosuppressive agent that provides higher freedom from acute and chronic rejection than cyclosporine after liver transplantation (LTx). Initially, a steroid-free state was observed in about 70% of patients at 1 year; this did not change over the next 5 years. The present study ident...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-200104270-00016
更新日期:2001-04-27 00:00:00
abstract::Organ shortage in liver transplantation has led the transplant community to expand the donor organ pool and reduce waiting list mortality by using so-called marginal donor or extended criteria donor (ECD) livers. The exact impact of these criteria on graft function and recipient survival are still under investigation....
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0b013e318186ad7a
更新日期:2008-10-15 00:00:00
abstract::Reports of early success with cryopreserved saphenous veins (CSV) as arterial conduits led us to develop cryopreserved iliac veins (CIV) as interposition grafts for portal vein reconstruction in living-related liver transplantation (LRLT). Despite encouraging short-term results, retrospective analysis of long-term cry...
journal_title:Transplantation
pub_type: 杂志文章,评审
doi:10.1097/00007890-199609270-00007
更新日期:1996-09-27 00:00:00
abstract:BACKGROUND:Human herpesvirus 6 (HHV-6) is susceptible to latency and reactivation in hematopoietic stem cell transplant (HSCT) recipients. We investigated the incidence of HHV-6 DNAemia and factors related to HHV-6 DNAemia and death after allogeneic stem cell transplantations. We also explored the relationship between ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0b013e318289958b
更新日期:2013-05-27 00:00:00
abstract:BACKGROUND:This study aimed at investigating the efficacy of the novel immunosuppressant FK778 to prevent the development and progression of chronic allograft vasculopathy (CAV). METHODS:Orthotopic aortic transplantations were performed in the PVG-to-ACI rat model and followed over the course of 120 days. Immunosuppre...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0b013e3181673608
更新日期:2008-03-27 00:00:00