Cell based therapies have been studied extensively in the context of transplantation tolerance induction. The most successful protocols have relied on transfusion of bone marrow prior to the transplantation of a renal allograft. However, it is not clear that stem cells found in bone marrow are required in order to render a transplant candidate immunologically tolerant. Accordingly, mesenchymal stem cells, regulatory myeloid cells, T regulatory cells, and other cell types, are being tested as possible routes to tolerance induction, in the absence of donor derived stem cells. Early data with each of these cell types have been encouraging. However, the induction regimen capable of achieving consistent tolerance, whilst avoiding unwanted sided effects, and which is scalable to the human patient, has yet to be identified. Here we present the status of investigations of various tolerogenic cell types and the mechanistic rationale for their use in in tolerance induction protocols.

Transplantation tolerance across histoincompatibilities in multiple non-H-2 minors (B10.BR into CBA/Ca) and minor plus H-2D (B10.A into CBA/Ca) antigens has been achieved successfully by combined adult bone marrow transplantation and treatment with CD4 and CD8 mAbs. The tolerant state was confirmed by permanent acceptance of donor strain skin grafts, and in vitro unresponsiveness to donor cells. Tolerance was associated with partial donor chimerism to various degrees. Tolerance to minor transplantation antigens induced in this manner was restricted to recipient-type MHC. The possibility was raised that tolerance resulted, at least in part, from clonal anergy rather than deletion.

From experimental observations on induction of transplantation tolerance, we discuss a model that accounts for tissue-specific tolerance to antigens not

Isolated from early blastocysts, embryonic stem (ES) cells capture the brief moment of pluripotency in the developing embryo, as evidenced by their differentiation into many somatic cell types in vitro. Although these properties might help meet the growing demand for spare parts to replace diseased or worn-out tissues, their use in so-called cell replacement therapy (CRT) poses several challenges, not least of which is the prevention of their subsequent rejection. Here we explore the notion that ES cells might spawn cell types necessary for the treatment of disease while acting as a plentiful source of hematopoietic stem cells (HSCs) or terminally differentiated dendritic cells (DCs) that might facilitate the induction of transplantation tolerance to the replacement tissues.

Chen, B and Splitter, G A., Monoclonal anti-lyt-1 antibodies militate transplantation tolerance by stimulating alloantigen specific lyt-1+ helper cells to produce il-2. Abstr. (1982). Subject Strain Bibliography 1982. 1728 ...

NIH Funding Opportunities and Notices in the NIH Guide for Grants and Contracts: Nonhuman Primate Transplantation Tolerance (U01) RFA-AI-16-007. NIAID

Originally aired on January 20, 2016 • 3:00 pm ET • Hosted by the Community of Basic Scientists DC-SIGN(+) Macrophages Control the Induction of Transplantation Tolerance (Link to abstract: a subscription to Journal of Experimental Medicine is required to view the full article, AST is not permitted to distribute the full text of the article) Author: Jordi Ochando, PhD • Mount Sanai School of Medicine Moderator: Heth R. Turnquist, PhD • University of Pittsburgh

TY - JOUR. T1 - Monocytic suppressive cells mediate cardiovascular transplantation tolerance in mice. AU - Garcia, M.R.. AU - Ledgerwood, L.. AU - Yang, Y.. AU - Xu, J.N.. AU - Lal, G.. AU - Burrell, B.. AU - Ma, G.. AU - Hashimoto, D.. AU - Li, Y.S.. AU - Boros, P.. AU - Grisotto, M.. AU - van Rooijen, N.. AU - Matesanz, R.. AU - Tacke, F. AU - Ginhoux, F.. AU - Ding, Y.Z.. AU - Chen, S.H.. AU - Randolph, GJ. AU - Merad, M.. AU - Bromberg, J.S.. AU - Ochando, J.C.. PY - 2010. Y1 - 2010. U2 - 10.1172/JCI41628. DO - 10.1172/JCI41628. M3 - Article. C2 - 20551515. VL - 120. SP - 2486. EP - 2496. JO - Journal of Clinical Investigation. JF - Journal of Clinical Investigation. SN - 0021-9738. IS - 7. ER - ...

Naturally occurring FOXP3(+) CD4(+) Treg have a crucial role in self-tolerance. The ability to generate similar populations against alloantigens offers the possibility of preventing transplant rejection without indefinite global immunosuppression. Exposure of mice to donor alloantigens combined with anti-CD4 antibody induces operational tolerance to cardiac allografts, and generates Treg that prevent skin and islet allograft rejection in adoptive transfer models. If protocols that generate Treg in vivo are to be developed in the clinical setting it will be important to know the origin of the Treg population and the mechanisms responsible for their generation. In this study, we demonstrate that graft-protective Treg arise in vivo both from naturally occurring FOXP3(+) CD4(+) Treg and from non-regulatory FOXP3(-) CD4(+) cells. Importantly, tolerance induction also inhibits CD4(+) effector cell priming and T cells from tolerant mice have impaired effector function in vitro. Thus, adaptive tolerance ...

Raging hormones are often blamed for the sometimes erratic behavior of teenagers; yet, hormonal fluctuations arent saddled with the stigma they deserve for altering biological behaviors in older adults. An example of such a phenomenon is the senescent immune system, which responds poorly to new stimuli. This failure may stem in part from the shrinking of the thymus that begins by puberty (thymic involution). However, in contrast to what one might intuit, this age-related muting of the immune response does not improve tolerance induction and reduce rejection after cell or organ transplantation. Instead, an active immune system is required to promote tolerance to novel antigens. Zhao et al. now show that modifying hormone concentrations can restore the induction of transplant tolerance in aged mice.. The authors found that after the age of 12 months, mice became resistant to tolerance induction for cardiac transplants. However, surgical castration led to long-term graft acceptance and restoration ...

Shoji T, Sahara H, Muniappan A, Guenther DA, Wain JC, Houser SL, Bravard MA, Pujara AC, Hasse RS, Sachs DH, Madsen JC, Allan JS. Operational tolerance to class I disparate lungs can be induced despite pretransplant immunization with class I allopeptides. Transplantation. 2007 Dec 15; 84(11):1467-73 ...

Control of immune damage at the effector phase is a crucial and perhaps the most realistic therapeutic target in clinical intervention of immune-mediated diseases (Chatenoud, 2011). Improvement of therapeutic interventions will require in-depth understanding of the immune cell behavior in target tissues and of the reaction of target tissue cells in response to insult. The current study suggests that the contact-dependent mode of immune cell interaction in the target tissue is a critical part of pathophysiology at the effector phase of immune responses, and immune tolerance induction may be facilitated by promoting intimacy between pathogenic and protective immune cells. In this regard, it is highly relevant that tissue antigen-specificity, as opposed to bystander killing (Tite and Janeway, 1984), shapes tissue fate in the effector phase.. With the tools currently available for longitudinal imaging of antigen-specific T cells in target tissues, we uncovered some basic behaviors of different ...

The identification and characterization of regulatory T (T(Reg)) cells that can control immune responsiveness to alloantigens have opened up exciting opportunities for new therapies in transplantation. After exposure to alloantigens in vivo, alloantigen-specific immunoregulatory activity is enriched in a population of CD4+ T cells that express high levels of CD25. In vivo, common mechanisms seem to underpin the activity of CD4+CD25+ T(Reg) cells in both naive and manipulated hosts. However, the origin, allorecognition properties and molecular basis for the suppressive activity of CD4+CD25+ T(Reg) cells, as well as their relationship to other populations of regulatory cells that exist after transplantation, remain a matter of debate..

Purpose: Our goal for this study was to determine the relative fates of endogenous Foxp3- conventional (Tconv) and Foxp3+ regulatory T cells (Tregs) specific for alloantigens as compared to non-antigen-specific T cells in the context of murine allotransplantation.. Methods: To selectively study alloreactive endogenous Tregs, donor hearts from F1 (BALB/cxC57BL/6) mice expressing the model antigen 2W were transplanted into C57BL/6 recipients, and 2W:I-Ab tetramers were used to track peripheral 2W:I-Ab-specific Tregs and Tconv cells. Long-term graft survival was induced in two groups of mice with co-stimulation blockade (CoB) comprising either anti-CD154 (D0, 7 and 14) + donor splenocytes (D0), or CTLA-4Ig (D0 and 2). Mice were sacrificed at D7 and D30, and their splenic T cells were phenotyped.. Results:Whereas the percentages or total numbers of 2W-reactive Tregs in secondary lymphoid organs were similar at d7 in naïve, acutely rejecting, and CoB-treated mice, at 30d post-transplant, recipients ...

Full text for this publication is not currently held within this repository. Alternative links are provided below where available. ...

Guest: Dr. Xunrong Luo, Instructor, Departments of Medicine and Pathology, Duke University School of Medicine; Director of Translation, Duke Transplant Center Topic: Transplantation state of the science, transplantation tolerance, immunosuppression, non-chimeric approach, new technologies in transplantation Xunrong Luo Duke faculty page Transplantation Tolerance through Hematopoietic Chimerism: Progress and Challenges for Clinical Translation article…

Downloading a figure as powerpoint requires a browser with javascript support. Enable javascript and try again For help please contact [email protected] ...

Slavin, S; Strober, S; Fuks, Z; and Kaplan, H S., Induction of specific tissue transplantation tolerance using fractionated total lymphoid irradiation in adult mice. Long- -term survival of allogeneic bone marrow and skin grafts. (1977). Subject Strain Bibliography 1977. 3748 ...

Skin is the most immunogenic component of a vascularized composite allograft (VCA) and is the primary trigger and target of rejection. The skin is directly accessible for visual monitoring of acute rejection (AR) and for directed biopsy, timely therapeutic intervention, and management of AR. Logically, antirejection drugs, biologics, or other agents delivered locally to the VCA may reduce the need for systemic immunosuppression with its adverse effects. Topical FK 506 (tacrolimus) and steroids have been used in clinical VCA as an adjunct to systemic therapy with unclear beneficial effects. However, there are no commercially available topical formulations for other widely used systemic immunosuppressive drugs such as mycophenolic acid, sirolimus, and everolimus. Investigating the site-specific therapeutic effects and efficacy of systemically active agents may enable optimizing the dosing, frequency, and duration of overall immunosuppression in

Vascularized Composite Allotransplantations (VCA) have become a clinical reality. However, broad clinical application of VCA is limited ...

2016 Annual Meeting: Topical Immunotherapy Synergizes with Systemic Immunotherapy to Prolong Survival of Vascularized Composite Allografts without Morbid Adverse Effects

2016 Annual Meeting: Locally Implantable Biodegradable Polymeric Tacrolimus Disc Prolongs Survival of Vascularized Composite Allografts without Morbid Adverse Effects

BACKGROUND: An increased percentage of peripheral transitional B cells producing IL-10 has been observed in patients tolerant to kidney allografts. In healthy volunteers, the balance between the CD40 and B cell receptor (BCR) signalling modulated IL-10 production by B cells, with stimulation via the BCR decreasing CD40-mediated-IL-10 production. In this study, we evaluate whether in tolerant kidney transplant patients the increased IL-10 production by B cells was due to an altered CD40 and/or BCR signalling.. METHODS: B cells obtained from a new cohort of tolerant renal transplant recipients and those from age- and gender-matched healthy volunteers, were activated via CD40 and BCR, either alone or in combination.. RESULTS: In tolerant patients we observed higher percentages of B cells producing IL-10 after CD40 ligation and higher expression of CD40L on activated T cells, compared to healthy controls. Furthermore, B cells from tolerant recipients had reduced ERK signalling following BCR-mediated ...

TY - JOUR. T1 - Analysis of neonatally induced tolerance of H-2 alloantigens - II. Failure to detect alloantigen-specific T-lymphocyte precursors and suppressors. AU - Gruchalla, Rebecca S.. AU - Streilein, J. Wayne. PY - 1982/3. Y1 - 1982/3. N2 - There is a considerable amount of evidence, confirmed and extended by our studies, in favor of clonal deletion of alloantigen-reactive cells in neonatally induced transplantation tolerance. We have demonstrated in adult mice bearing long-standing skin allografts that lymphocytes specifically reactive with the tolerated H-2 alloantigens are undetectable by mixed lymphocyte and graftversus-host reactions, and in cell-mediated lympholysis. In addition, lymphoid cells capable of suppressing the reactivity of syngeneic normal lymphocytes in these assays similarly escape detection. Moreover, putative precursors of T cells specific for the tolerated antigens cannot be activated polyclonally with concanavalin A (Con A), nor can they be identified among ...

Farrowing induction in sows is frequently applied and different protocols were described. Most studies induce farrowing between day 111 and 113 of gestation, but hardly any later during gestation. The aim of this study was to investigate the effects of different induction protocols when applied on d114 of gestation. We randomly assigned 118 sows to four treatment groups: single injection of prostaglandin (1×PG), prostaglandin combined with oxytocin 24 hours later (PG+OT), half the dosage of prostaglandin twice with six hours interval (2×1/2PG), and a control group of which farrowing wasnt induced. All injections were administered intramuscularly in the neck on day 114 of gestation. A significantly higher percentage of sows started farrowing between 22 and 32 hours after induction in the PG+OT-group (68 per cent) and the 2×1/2PG-group (52 per cent) compared to the control group (23 per cent). The 1×PG-group (46 per cent) tended to differ from the control group (P=0.087). More sows from the ...

Alloreactive T cells are core mediators of graft rejection and are a potent barrier to transplantation tolerance. It was previously unclear how T cells educated in the recipient thymus could recognize

LIDSEN series of journals are published by LIDSEN Publishing Inc, a non-profit scholarly Open Access publisher focused on biological, biomedical and medical studies. We aim to select ground-breaking research based on novelty, timeliness, scientific significance, potential audience interests, etc. We strive to provide an easily and freely accessible platform to researchers and practitioners in support of their novel and valuable ideas.

Searching For The Secrets Of Drug-Free Transplants: University Of Pittsburgh, Through Immune Tolerance Network, To Develop Tests Predictive Of Transplant Tolerance

For individuals who sustain devastating composite tissue loss, vascularized composite allotransplantation (VCA; e.g., hand and face transplantation) has the potential to restore appearance and function of the damaged tissues. As with solid organ transplantation, however, rejection must be controlled by multidrug systemic immunosuppression with substantial side effects. As an alternative therapeutic approach inspired by natural mechanisms the body uses to control inflammation, we developed a system to enrich regulatory T cells (Tregs) in an allograft. Microparticles were engineered to sustainably release TGF-β1, IL-2, and rapamycin, to induce Treg differentiation from naïve T cells. In a rat hindlimb VCA model, local administration of this Treg-inducing system, referred to as TRI-MP, prolonged allograft survival indefinitely without long-term systemic immunosuppression. TRI-MP treatment reduced expression of inflammatory mediators and enhanced expression of Treg-associated cytokines in ...

Mice given short courses of anti-CD4 and anti-CD8 monoclonal antibodies became tolerant of allogeneic skin grafted at the same time. Tolerance could be obtained without T cell depletion across multiple minor antigen mismatches, both in naive and primed animals, demonstrating that peripheral T cells could be tolerized, even if they had been previously activated. Where donor and recipient were incompatible across the whole major histocompatibility complex, specific tolerance could be achieved by using a combination of depleting followed by non-depleting antibodies, where each alone was unsuccessful. Although mice clearly tolerated their original skin grafts, we observed in some strain combinations that a second fresh, but genotypically identical graft, was slowly rejected. Such mice also possessed T cells which could proliferate to donor-type stimulator cells in vitro. Whatever the mechanisms, we have demonstrated that operational transplantation tolerance can be achieved with simple, non-toxic antibody

Purpose: Transplantation of faces, hands, and limbs using vascularized composite allotransplantation (VCA) has faced significant challenges hindering its routine implementation in the clinic. One critical hurdle is the scarcity of adequately matched HLA donors, requiring high doses of immunosuppressants which prevent rejection, but also present significant risks to the patient. New methods of controlling rejection are desperately needed. One possibility could be in exploiting the links between the nervous and immune systems that regulate host defense. The neurotransmitter norepinephrine acts through the β2-adrenergic receptors (β2-AR) to regulate immune cells resulting in immunosuppression. We hypothesize that β2-AR activation suppresses immune cell function after VCA.. *Methods: Heterotopic hind limb transplantation mouse model was used with C57BL/6 (H-2b) as recipients and BALB/c (H-2d) mice as donors. Graft survival was measured with and without treatment with the β2-agonist terbutaline, ...

TY - JOUR. T1 - Review of the early diagnoses and assessment of rejection in vascularized composite allotransplantation. AU - Starzl, Ravi. AU - Brandacher, Gerald. AU - Lee, W. P.Andrew. AU - Carbonell, Jaime. AU - Zhang, Wensheng. AU - Schnider, Jonas. AU - Gorantla, Vijay. AU - Schneeberger, Stefan. AU - Zheng, Xin Xiao. PY - 2013. Y1 - 2013. N2 - The emerging field of vascular composite allotransplantation (VCA) has become a clinical reality. Building upon cutting edge understandings of transplant surgery and immunology, complex grafts such as hands and faces can now be transplanted with success. Many of the challenges that have historically been limiting factors in transplantation, such as rejection and the morbidity of immunosuppression, remain challenges in VCA. Because of the accessibility of most VCA grafts, and the highly immunogenic nature of the skin in particular, VCA has become the focal point for cross-disciplinary approaches to developing novel approaches for some of the most ...

Dr. Sachs major areas of research are the following:. A. Induction of transplantation tolerance:. A major thrust of transplantation research in this laboratory has been directed toward induction of tolerance as a means of permitting transplantation of organs to be achieved without a requirement for immunosuppressive drugs. Two major models for tolerance induction are studied:. 1) Regulatory tolerance: Using miniature swine with defined MHC haplotypes (see below), Dr. Sachs and colleagues demonstrated that a short course of immunosuppression with a high-dose of calcineurin inhibitors is capable of inducing long-term tolerance in juvenile animals. This phenomenon has become and remains an important basic model for the study of tolerance induction across MHC barriers in a large animal model. Among active studies being carried out in this model are: a) the role of the thymus in permitting regulatory tolerance to develop; b) the dependence of tolerance on T regulatory cells; c) the adoptive transfer ...

This Research Topic is a call for papers to provide an up to date assessment of current attempts to introduce tolerogenic therapies into clinical practice. Tolerance has been a highly sought after goal in the field of organ transplantation for over half a century, and is now readily achievable in rodent models, but considerable barriers remain to successfully translating tolerogenic treatments to the clinic. The initial call for this Research Topic has been aimed to provide an overview of recent advances made within the European RISET and American ITN networks with regard to tolerogenic strategies in clinical transplantation, autoimmune disease, and allergy. Articles will also cover the barriers to clinical tolerance induction and new emerging approaches to overcome such barriers. 1. Collaborative networks working towards the goal of therapeutic tolerance induction 2. Prope tolerance and minimization of immunosuppression 3. Lessons from operationally tolerant patients 4.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details ...

Plenary Session: Reprogramming the Immune System in Autoimmunity and Transplantation VIEW PRESENTATION Herman Waldmann is currently Emeritus Professor of Pathology, and formerly Head of the Sir William Dunn School in Oxford. He qualified in medicine in 1971, and then began his scientific career in Cambridge where he studied mechanisms by which cells of the immune system could interact to mount immune responses. During this period he developed new methods of measuring the frequencies of cells specific for antigen. This early work led him to become interested in immunological tolerance and achieving tolerance for therapeutic purposes. Soon after the discovery of monclonal atibodies Waldmann spent a short sabbatical with Milstein where he began to develop rat monoclonal antibodies to mouse and human lymphocytes. From 1980 he has been funded by an MRC Programme Grant to study mechanisms of transplantation tolerance and strategies to achieve this both experimentally and clincially. In 1989 the ...

LITTMUS is a clinical research study testing a new approach to achieve transplant tolerance using the liver transplant recipients own T regulatory cells (Tregs ...

The Immune Tolerance Network is dedicated to the clinical evaluation of novel tolerance-inducing therapies that will ¿re-educate¿ the immune system to eliminate injurious immune responses. The ITN is conducting clinical trials in autoimmune diseases such as Type 1 Diabetes. In addition, to understand the underlying mechanisms of action of the candidate therapies and to monitor tolerance, the ITN has established state of the art core laboratory facilities to conduct integrated mechanistic studi...

Current Transplant Research projects include: immunotherapy, transplant tolerance, organ preservation, growth factor biology and bioengineering.

In liver transplantation up to 20% of recipients can completely discontinue immunosuppressive therapy maintaining normal graft function, and are conventionally considered as operationally tolerant. Discontinuation of immunosuppressive drugs in operationally tolerant recipients could lessen the side effects of chronic immunosuppressive therapy. However, this strategy results in the development of rejection in a high proportion of recipients who require lifelong immunosuppression. Thus, there is a need to identify predictive factors of successful drug withdrawal and to define the clinical and histological outcomes of operationally tolerant liver recipients.. The main objective of this study is to establish the safety of attempting immunosuppressive (IS) drug withdrawal in stable liver transplant recipients, using standard clinical, biological and histopathological methods, to screen and follow-up patients, and to confirm the benefit of maintaining immunosuppressive drug interruption in patients ...

Curing type 1 diabetes by islet transplantation requires overcoming both allorejection and recurrent autoimmunity. This has been achieved with systemic immunosuppression, but tolerance induction would be preferable. Most islet allotransplant tolerance induction protocols have been tested in nonobese diabetic (NOD) mice, and most have failed. Failure has been attributed to the underlying autoimmunity, assuming that autoimmunity and resistance to transplantation tolerance have a common basis. Out of concern that NOD biology could be misleading in this regard, we tested the hypothesis that autoimmunity and resistance to transplantation tolerance in NOD mice are distinct phenotypes. Unexpectedly, we observed that (NOD x C57BL/6)F(1) mice, which have no diabetes, nonetheless resist prolongation of skin allografts by costimulation blockade. Further analyses revealed that the F(1) mice shared the dendritic cell maturation defects and abnormal CD4(+) T cell responses of the NOD but had lost its defects in

A paradigm shift in immunology has been the recent discovery of regulatory T cells (T reg cells), of which CD4(+)Foxp3(+) cells are proven as essential to self-tolerance. Using transgenic B6.Foxp3(hCD2) mice to isolate and ablate Foxp3(+) T reg cells with an anti-hCD2 antibody, we show for the first time that CD4(+)Foxp3(+) cells are crucial for infectious tolerance induced by nonablative anti-T cell antibodies. In tolerant animals, Foxp3(+) T reg cells are constantly required to suppress effector T cells still capable of causing tissue damage. Tolerated tissue contains T cells that are capable of rejecting it, but are prevented from doing so by therapeutically induced Foxp3(+) T reg cells. Finally, Foxp3(+) cells have been confirmed as the critical missing link through which infectious tolerance operates in vivo. Peripherally induced Foxp3(+) cells sustain tolerance by converting naive T cells into the next generation of Foxp3(+) cells. Empowering Foxp3(+) regulatory T cells in vivo offers a tractable

Successful induction of allograft tolerance has been achieved in nonhuman primates (NHPs) and humans via induction of transient hematopoietic chimerism. Since allograft tolerance was achieved in these recipients without durable chimerism, peripheral mechanisms are postulated to play a major role. Here, we report our studies of T cell immunity in NHP recipients that achieved long-term tolerance versus those that rejected the allograft (AR). All kidney, heart, and lung transplant recipients underwent simultaneous or delayed donor bone marrow transplantation (DBMT) following conditioning with a nonmyeloablative regimen. After DBMT, mixed lymphocyte culture with CFSE consistently revealed donor-specific loss of CD8+ T cell responses in tolerant (TOL) recipients, while marked CD4+ T cell proliferation in response to donor antigens was found to persist. Interestingly, a significant proportion of the proliferated CD4+ cells were FOXP3+ in TOL recipients, but not in AR or naive NHPs. In TOL recipients, ...

Regardless of the MHC mismatching, all animals displayed high-level chimerism at all time points in lymphoid (50-70%), myeloid (40-80%) and granulocyte (40-80%) lineages. MHC Class II-mismatched chimeras remained tolerant of VCAs, without significant histological or clinical features of rejection at any time-point. In contrast, both MHC Class I-mismatched animals experienced acute rejection crises of the epidermal component of the VCAs following tapering of immunosuppression, with one of these animals mounting recurrent rejection episodes. Histological visualization confirmed that rejection was confined to skin epidermis. In vitro assays in all animals demonstrated donor-specific non-responsiveness at all points, including after rejection crises, suggesting that the epidermal rejection in the MHC class I-mismatched animals was a local effect ...

Thomas S. Zimmer Professor of Reconstructive Surgery (in Pediatrics) (212) 305-9691 Dr. Emond is the Vice Chairman of Surgery and Chief of the Transplantation Services at Columbia University. He has over30 years of experience performing liver transplantation and complex liver and biliary surgery in children and adults, including the first living donor liver transplantation (LDLT) in the United States. Dr. Emond has published extensively in this field and was a co-chair of the NIH A2ALL program for 13 years. In collaboration with the department of Medicine at Columbia, Dr. Emond recruited the leadership of the Columbia Center for Translational immunology that created the foundation for translational and clinical research in transplantation tolerance. This will lead the way to inducing transplant tolerance in liver patients with the mixed chimerism strategy. As Director of Transplantation at the Columbia University Medical Center Dr. Emonds activities foster clinical excellence and research across all 11

The Enzyme-Linked ImmunoSpot (ELISPOT) assay is a widely used method for monitoring cellular immune responses in humans and other animals, and has found clinical applications in the diagnosis of tuberculosis and the monitoring of graft tolerance or rejection in transplant patients. The ELISPOT technique has proven to be among the most useful means available for monitoring cell-mediated immunity, due to its sensitive and accurate detection of rare antigen-specific T cells (or B cells) and its ability to visualize single positive cells within a population of peripheral blood mononuclear cells (PBMCs). The ELISPOT method was developed by Cecil Czerkinskys group in Gothenburg, Sweden in 1983, for the purpose of detecting antigen-specific antibody-secreting cells (ASC) in a B cell ELISPOT assay, which was a modification of a traditional sandwich ELISA immunoassay. The ELISPOT assay has since been more widely adopted for the identification and enumeration of cytokine-producing cells at the single ...

Short Course Immune Induction Therapy or SCIIT, is a therapeutic strategy employing rapid, specific, short term-modulation of the immune system using a therapeutic agent to induce T-cell non-responsiveness, also known as operational tolerance. As an alternative strategy to immunosuppression and antigen-specific tolerance inducing therapies, the primary goal of SCIIT is to re-establish or induce peripheral immune tolerance in the context of autoimmune disease and transplant rejection through the use of biological agents (compare also tolerogenic therapy). In recent years, SCIIT has received increasing attention in clinical and research settings as an alternative to immunosuppressive drugs currently used in the clinic, drugs which put the patients at risk of developing infection, cancer, and cardiovascular disease. Immune tolerance can be defined as the ability of the immune system to distinguish between self and non-self, or harmless and harmful. T-cells are able to distinguish between self and ...

The procedures for preservation of human donor skin with glycerol, as applied by the Euro Skin Bank (ESB), were evaluated against the prEN 12442 standard: animal tissues and their derivatives used in the manufacture of medical devices. The focus chosen for this review is on risks related to the transmission of diseases. Product-related hazards were identified. Subsequently, the associated risks and the ESB measures to reduce these risks were discussed. The acceptability of the residual risks was also evaluated by comparing the risk-reducing measures with the prEN 12442, EN 1441, EN 1174 and ISO 14160 standards. Conclusions drawn indicate that ESB procedures as they now stand do not meet all the requirements of these standards. Nonconformities were used to formulate a validation plan containing considerations and suggestions on process definition and control, as well as an assessment of bacteriological and virological inactivation and/or elimination. The implementation of this plan should lead to ...

Vascularized composite allografts (VCAs) are transplants involving several types of tissue. The best-known VCAs are hand, arm, and face transplants, but doctors have also successfully transplanted other parts like abdominal walls and voice boxes. Use the free resources below to learn more about VCAs or to educate others about these exciting innovations in transplant science. For additional information about Vascularized Composite Allograft organ transplants, see the Face and Hands Transplants page.

An innovative Northwestern Medicine® research program investigating if stem cells may be the key to allowing organ transplant patients to stop taking

HLA-G was described originally as a tolerogenic molecule that allows the semiallogeneic fetus to escape from recognition by the maternal immune response. This review will discuss different steps in the study of HLA-G expression and functions in vivo, starting with analyses of expression of the HLA-G gene and its receptors in transgenic mice, and continuing with applications of HLA-G and its receptors in prevention of allograft rejection, transplantation tolerance, and controlling the development of infection. Humanized mouse models have been discussed for developing in vivo studies of HLA-G in physiological and pathological conditions. Collectively, animal models provide an opportunity to evaluate the importance of the interaction between HLA-G and its receptors in terms of its ability to regulate immune responses during maternal-fetal tolerance, survival of allografts, tumor-escape mechanisms, and development of infections when both HLA-G and its receptors are expressed. In addition, in vivo studies on

Vascularized Composite Allograft refers to the transplantation of non-autologous vascularized peripheral tissues including skin, muscle, nerve, tendon and/or bone as a functional unit (e.g., a hand) to replace non-reconstructible tissue defects.. VCA is viewed as one field that can be driven by orthopedic surgery, plastic surgery, or transplantation surgery. The complexity of VCA mandates that this procedure be driven by surgeons and considered as an organ from a regulatory standpoint.. ...

Upper extremity transplantation is an innovative reconstructive strategy with potential of immediate clinical application and the most near-term pay-off for select amputees, allowing reintegration into employment and society. Routine applicability and widespread impact of such strategies for the upper extremity amputees with devastating limb loss could be enabled by implementation of cellular therapies that integrate and unify the concepts of transplant tolerance induction with those of reconstructive transplantation. Such therapies offer the promise of minimizing the risks, maximizing the benefits and optimizing outcomes of these innovative procedures.

Noninherited maternal antigens identify acceptable HLA mismatches: Benefit to patients and cost-effectiveness for cord blood banks. Biology of Blood and Marrow Transplantation. 2014 ...

An amphetamine tolerance can cause a person to take more amphetamines than they really need, and can cause their body to become dependent then addicted.

The Immune Tolerance Network seeks to provide funding and strategic support for clinical trials designed to induce immune tolerance in allergy and asthma, autoimmune disease, transplantation, and type 1 diabetes. The ITN is currently seeking proposals for clinical trials of immune tolerance in transplantation using deceased-donor organs.

A 3-Year Program From the Turkish Ministry of Health for Standardization and Service Quality Improvement of Transplant and Tissue Typing Laboratories in Turkey. Bilkay Baþtürk, Ferzane Mercan, Arif Kapuaðasi, Fatma Savran Oðuz, Gülderen Yanikkaya Demirel, Ýbrahim Mehmet Ali Öktem, Avþar Aslan, Serap Yýlmaz, Nurullah Okumuþ, Eyüp Gümüþ. Online Publication Date : Jun 28 ...

d. Diminution in the physiological response to a drug that occurs after continued use, necessitating larger doses to produce a given response ...