ISSN:1087-2418    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Anti-CD4 monoclonal antibody (mAb) has been used extensively in transplant animal models. Adjunctive peri-operative administration of anti-CD4 mAb, in combination with other modalities, was able to induce donor-specific tolerance in the vast majority of recipients who had undergone grafting. The putative tolerogenic mechanisms are complex, and involve both central and peripheral immune regulatory pathways.In vitrotreatment of T cells with nondepleting anti-CD4 mAbs resulted, upon restimulation, in either CD4+ T-cell anergy or T-helper 2–type immune deviation. Studies of signal transduction pathways of T-cell activation illustrate the coreceptor function of CD4 molecules and provide the biochemical basis of the functional consequences of the CD4 blockade. Lymphocytes from anti-CD4–treated animals or lymphocytes culturedin vitroexhibited some common characteristics. In addition, researchers have been particularly interested in detecting an operational, infectious tolerance mechanism regulated by regulatory CD4+ T cellsin vivo. The improved understanding of this type of tolerance and the role of regulatory CD4+ T cells should lead to the development of novel therapeutic strategies, based on new concepts of immunosuppression in transplant recipients.

ISSN:1087-2418    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

An area of considerable interest in current transplantation immunology is the role of costimulatory molecules in the development of the immune response. One specific costimulatory receptor:ligand interaction that has been the object of extensive investigation is that of CD40:CD154. This interaction has been implicated in T cell and antigen-presenting cell activation, and in the pathogenesis of allograft rejection. This review examines recent progress made in our understanding of these important costimulatory molecules, and their potential relevance to therapeutic immunosuppression.

ISSN:1087-2418    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Central to the events of T-cell activation and acute allograft rejection is the production of T-cell growth factors, a family of cytokines with potent mitotic activities (ie, interleukin-2, -4, -7, -9, and -15) that drive the proliferation, clonal expansion, and functional maturation of alloreactive T cells. Thus, targeting T-cell growth factors or their receptor components remains one of the key aspects of transplantation immunology. However, there is compelling evidence that T-cell growth factors also regulate the acquisition of peripheral allograft tolerance through modulating apoptotic cell death of activated T cells and guiding the development of immune regulatory cells. Thus, understanding the individual and collective role of T-cell growth factors in allograft response may prove to be critically important in designing effective therapeutic strategies to promote transplantation tolerance.

ISSN:1087-2418    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

T-cell recognition of allopeptides presented either by recipient or donor major histocompatibility complex molecules represents a key component for the initiation of T-cell responses to alloantigens. However, the mechanisms by which this presentation occurs continue to be a source of debate and have received considerable attention in the literature over the past few years. Better understanding of the mechanisms of allorecognition is essential for the future development of specific immunotherapies and novel approaches for the induction of transplantation tolerance. This article reviews recent publications that represent advances made in our understanding of T-cell allorecognition and its role in allograft rejection.

ISSN:1087-2418    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Advances in immunotoxin formulation have enabled application of this reagent to tolerance induction in primate preclinical models. The most successful paradigm transiently ablates recipient T cells, enabling engraftment into an immunologically permissive environment. The greatest success in stable tolerance induction (without chronic rejection) has been with the combination of immunotoxin and 15-deoxyspergualin. 15-deoxyspergualin complements immunotoxin by reducing cytokine production and blocking dendritic cell maturation and antigen presentation. Thus, we have been able to establish durable, long-term immunologic T- and B-cell tolerance (without donor-specific alloimmunity) to MHC-mismatched macaque allografts, satisfying the most stringent criteria for true toilerance.

ISSN:1087-2418    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Apoptosis or programmed cell death (PCD) is a physiological and pathological process of seminal importance to virtually all systems of the body. Programmed cell death is involved in mechanisms of immune cytotoxicity, immune regulation and ischemia-reperfusion injury processes central to tissue and organ transplantation. To date, PCD has been shown to be involved in diverse areas, including liver and islet graft preservation during procurement and transplant; transplant organ damage and rejection of liver, heart, kidney, islet, and intestine grafts; and immune tolerance. In addition to central tolerance, at least two systems of peripheral immune tolerance, the veto cell mechanism and the costimulation blockade, clearly involve PCD. Virtually all well studied systems generating immunodeviation and normal immunoregulation depend to some degree on PCD. Thus, the potential for therapeutic immunomodulation using PCD-directed therapy is enormous. Progress in understanding crucial mechanisms of PCD, such as caspase activity, proteosome function, and Fas/Fas ligand, TRAIL-R/TRAIL, and TNF/TNFR-1 and -2 signaling pathways, as well as mechanisms of inhibition of both type I and type II pathways of PCD among the various functional immune cells, will be critical for targeting future immunomodulation therapies for transplantation.

ISSN:1087-2418    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The acquisition of transplantation tolerance is an active, highly regulated, and multistep process. In this review, we critically examine the validity and limits of the Th1/Th2 paradigm during the period of tolerance induction. We emphasize that host response to major histocompatibility complex–mismatched allografts encompasses an unusually large population of T-cell clones and involves both direct and indirect recognition of foreign major histocompatibility complex antigen. Thus, control of robust expansion of alloaggressive T-cell clones and proliferation is a critical initial step in the acquisition of transplantation tolerance.

ISSN:1087-2418    

出版商:OVID    

年代:2000

数据来源: OVID