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 donor-specific cytotoxic T cells mediate graft rejection in high-risk, but not normal, eyes. MHC plus minor histoincompatible C57BL/6 corneas were grafted orthotopically onto BALB/c mice. Healthy recipient eyes were trephined and served as normal graft beds; corneal vascularization was induced by penetrating sutures and these eyes served as 'high-risk' graft beds. Cytotoxic T cells were assayed at 2 and 8 weeks postgrafting using either draining cervical lymph nodes or spleen cells restimulated for 3 days with irradiated allogeneic splenic stimulator cells. As a positive control, donor-specific cytotoxic T cells were induced in mice immunized by subcutaneous injection of allogeneic spleen cells. A low percentage (only 50%) of corneal allografts were rejected when placed orthotopically onto normal healthy eyes. Donor-specific cytotoxic cells were not detected in the draining lymph nodes or spleens of mice that either accepted, or rejected their corneal graft. The failure to detect cytotoxic T cells was not due to anergy or the deletion of allospecific precursors of cytotoxic T cells. By contrast, 97% of corneal allografts were rejected from high-risk recipient eyes (no immune privilege). Donor-specific cytotoxic T cells were routinely detected in the draining lymph nodes of these mice and their appearance coincided with graft rejection. We conclude that allografts placed onto normal healthy eyes fail to induce donor-specific cytotoxic T cells. In the absence of specific cytotoxic T cells, other alloimmune effectors are less successful at mediating rejection. By contrast, allografts placed onto high-risk eyes induce donor-specific cytotoxic T cells, and all grafts are universally rejected. These results imply that immune privilege can protect corneal allografts from most effector mechanisms, except cytotoxic T cells.
journal_name
Transpl Immunoljournal_title
Transplant immunologyauthors
Ksander BR,Sano Y,Streilein JWdoi
10.1016/s0966-3274(96)80034-7subject
Has Abstractpub_date
1996-03-01 00:00:00pages
49-52issue
1eissn
0966-3274issn
1878-5492pii
S0966-3274(96)80034-7journal_volume
4pub_type
杂志文章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::The outcome of hyperacute grade 3-4 steroid-refractory graft-versus-host-disease (SR-GVHD) remains dismal despite a plethora of agents being tried alone or in combination. Following T replete haploidentical transplantation with post-transplantation cyclophosphamide on 75 patients, 10 patients (13%) aged 2-20years, dev...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2016.08.009
更新日期:2016-11-01 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::The novel immunosuppressive agents malononitrilamides (MNA) 279 and 715 are derivatives of A77 1726, the primary metabolite of leflunomide. The effects of these agents have been previously demonstrated in rat skin and cardiac allo- and xenotransplant models. The aim of this study was to evaluate the combination of MNA...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(99)80036-7
更新日期:1999-09-01 00:00:00
abstract::Adhesion molecule expression is an important event during early transplant failure. The aim of the present study was to examine the release of adhesion molecules during the first minutes of kidney allograft reperfusion in relation to delayed graft function and acute graft rejection. We enrolled 49 renal transplant rec...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2006.08.002
更新日期:2006-11-01 00:00:00
abstract::Graft rejection and graft-versus-host disease are leading causes of transplant related mortality despite advancements in immunosuppressive therapy. Mesenchymal stem cells (MSCs) offer a promising addition to immunosuppressive drugs (ISD), while NK-cells are increasingly used as effector cells in graft-versus-leukemia....
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2016.04.008
更新日期:2016-07-01 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::B(io) B(reedding)/O(ttawa) K(alsburg) rats spontaneously develop insulin-dependent type 1 diabetes. Days before BB/OK rats become diabetic, their body seems to be flabby which may be attributed to loss of subcutaneous fat. However, the rats are normoglycemic and manifest 3-4 days later. This observation prompted us to...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2011.01.003
更新日期:2011-05-01 00:00:00
abstract::FTY720 alters lymphocyte recirculation and homing by interfering with S1P receptors on lymphocytes, possibly in combination with chemokine receptors, and induces a decrease in PBL counts. In fresh, whole blood samples of 14 kidney transplant patients, we analyzed by flow cytometry the effect of FTY on the number of NK...
journal_title:Transplant immunology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.trim.2006.02.002
更新日期:2006-04-01 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::Chronic allograft dysfunction is one of the most important reasons for late graft loss after renal transplantation. Its etiology is multifactorial and combines immunological as well as non-immunological mechanisms. It is known from large registry data that MHC mismatches are inversely correlated to long term allograft...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2009.09.007
更新日期:2010-02-01 00:00:00
abstract:AIM:To identify the frequency of exposure to sensitizing factors and evaluate the risk ascribable to each sensitizing factor generating HLAabs measured by Luminex. METHODS:This is a retrospective cohort study that included 502 transplanted patients and 51 patients on the waiting list for a deceased donor graft. Patien...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2016.08.003
更新日期:2016-09-01 00:00:00
abstract::In recent years, the utility of vascular complement factor 4d (C4d) deposition as diagnostic tool for antibody mediated rejection (AMR) after lung transplantation, has become a controversial issue. We aimed to pinpoint the problematic nature of C4d as biomarker with a simple experiment. We quantified C4d in broncho-al...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2020.101352
更新日期:2021-02-01 00:00:00
abstract::Despite improvements in the prevention and treatment of graft-versus-host disease (GvHD) this allogeneic immune response is still one of major complications following allogeneic stem cell transplantation (SCT). Identification of patients at risk for the development of acute and chronic GvHD would facilitate early inte...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2012.07.003
更新日期:2012-12-01 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::Keratinocytes are activated to express MHC class II and ICAM-1 molecules during cutaneous inflammatory reactions. It is controversial how the interaction between these 'nonprofessional' antigen presenting cells (APC) and infiltrating T cells affects the local inflammatory response. To address this issue we analyzed wh...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/0966-3274(93)90059-h
更新日期:1993-01-01 00:00:00
abstract::Although the clinical significance of anti-HLA antibodies in heart and lung transplantation is less well studied than in renal transplantation, several studies have shown that heart and lung recipients transplanted in the presence of donor-specific antibodies are at increased risk for early acute rejection and have a ...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/j.trim.2004.01.005
更新日期:2004-06-01 00:00:00
abstract::We investigated the immunosuppressive effects of the dihydroortate dehydrogenase (DHODH) inhibitor compounds ABR-222417 and ABR-224050 from Active Biotech (Sweden). We verified the inhibitory effects of these compounds on the proliferation of CD4(+) and CD8(+) T-cells in vivo by using superantigen staphylococcus enter...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2010.05.005
更新日期:2010-08-01 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::Gene polymorphisms of cytotoxic T lymphocyte associated antigen 4 (CTLA4) play an influential role in the graft rejection and long-term clinical outcome of organ transplantation. We investigated the associations of five CTLA4 single nucleotide polymorphisms (SNPs) (rs733618T/C, rs4553808A/G, rs5742909C/T, rs231775G/A,...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2012.02.005
更新日期:2012-06-01 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::Induction of donor-specific hyporesponsiveness would minimize the need for intensive immunosuppression in the clinical setting of graft rejection and dendritic cells (DCs) might be useful tools for this purpose. Besides their ability to induce immunogenic T-cell responses, these antigen presenting cells can lead to T-...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2006.03.001
更新日期:2006-06-01 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:INTRODUCTION:Regulatory T cells (Tregs) have been related to acute rejection as have the cytotoxic T cells, their immunological counterpart. High expression of cytotoxic markers has been related to acute rejection incidents following both kidney and intestine transplantation, while the correlation between FoxP3 express...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2010.06.011
更新日期:2010-10-01 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::Type 1 diabetes is one of the more costly chronic diseases of children and adolescents throughout North America and Europe, exhibiting an average estimated prevalence rate of nearly 0.2%. It occurs in genetically predisposed individuals when the immune system attacks and destroys specifically the insulin-producing bet...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/j.trim.2003.12.011
更新日期:2004-04-01 00:00:00
abstract::This study provides data on HLA-A, -B, and -DRB1 frequencies among 861 end-stage renal disease (ESRD) patients from Croatia and estimates the benefit of the kidney exchange program by comparing HLA distribution and assessing HLA mismatches (MMs) within a group of ESRD patients who received kidney grafts from 707 cadav...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2020.101318
更新日期:2020-10-01 00:00:00
abstract::Cellular and antibody-mediated rejection processes and also interstitial fibrosis/tubular atrophy (IFTA) lead to allograft dysfunction and loss. The search for accurate, specific and non-invasive diagnostic tools is still ongoing and essential for successful treatment of renal transplanted patients. Molecular markers ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2016.09.003
更新日期:2016-11-01 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::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