ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Experimental clinical evidence has highlighted the importance of early posttransplantation events in determining allograft survival. Graft inflammation is initiated by activation of cellular and humoral components of innate immunity in an antigen-independent manner. Subsequently, the alloreactive response is driven by donor-specific T-cell–dependent adaptive immunity. A positive cross-talk between innate and adaptive responses governs the magnitude of the host-versus-graft response. This article reviews recent studies on the cellular and molecular pathways through which innate immunity may trigger allograft rejection.

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Having been a taboo subject for many years, dedicated regulatory T cells are now center stage. To the transplantation immunologist, this should not come as a surprise, given that transferable T-cell tolerance has remained a robust phenomenon over the past 2 decades. Recent insights into the cell populations mediating this regulation and, to a limited extent, into their mechanisms of action have heightened interest in the possibility of deliberately inducing such cells with specificity for donor alloantigens, as a means of promoting transplantation tolerance. This review discusses the range of regulatory T cells that have been reported, and the complementary roles of deletion and regulation in the development of tolerance to transplanted tissues.

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The impact of memory T cells on graft rejection and tolerance induction in transplant recipients is well recognized, particularly in clinical settings. This review discusses how alloreactive memory T cells are generated, either directly by alloantigen sensitization or indirectly by cross-reactive memory T cells against environmental antigens. Examples are provided of memory T-cell resistance to one of the most effective tolerance induction strategies today,ie, costimulation blockade, followed by a literature review on the role of memory T cells, especially of CD8 phenotype, in host immunity. The generation of distinct memory T-cell subsets, their different costimulation requirements for activation, and homeostasis are analyzed in the context of novel therapeutic strategies. Thus, modifications in current immunosuppressive regimens or adjunctive use of new agents is needed to control memory T-cell–mediated transplant rejection successfully. Indeed, comprehensive basic research on alloreactive memory T cells is warranted to develop much-needed specific strategies to overcome this seemingly formidable obstacle in the allograft rejection cascade.

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Allograft rejection-like tolerance is a T-cell–mediated event. Acquisition of transplant tolerance, however, is a learned process, and T cells need to engage actively in alloantigens to learn to tolerate the graft. T-cell growth factors play an important role in regulating multiple aspects of the allograft response. It is true that T-cell growth factors can drive clonal expansion and functional maturation of alloreactive T cells; therefore, targeting growth factors and their receptor components remains one of the key aspects in transplantation. There is compelling evidence that growth factors also regulate the induction of peripheral allograft tolerance through programming activated T cells for apoptosis and guiding the development of regulatory T cells. Thus, understanding precisely the role of T-cell growth factors in regulating T-cell homeostasis and in developing active immune regulation is critically important in transplant tolerance.

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

T-cell costimulation through the B7/CD28 and CD40/CD154 pathways plays a critical role in mediating the immune response to a transplanted graft. In addition, an increasing number of novel costimulatory pathways have recently been described. These pathways fall into either the B7/CD28 family or the tumor necrosis factor (TNF)/tumor necrosis factor receptor (TNF-R) family of molecules and can serve to stimulate or regulate alloimmune responses. These molecules both act independently and interact in a complex fashion to modulate alloresponses, and serve as potential targets for agents to block graft rejection and induce tolerance.

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

In vitrodata point to dendritic cells having a key role in development of immune responses, but in the context of organ transplantation, it could be argued that there is surprisingly little evidence currently available to support the attention these cells receive. A general schema is available from other contexts but often leads to confusion between what is suggested should occur and what is known to occur experimentally. Conceptually, in unmodified recipients, donor dendritic cells migrate from the graft to host lymphoid tissues and stimulate host alloresponses, which can eventually lead to graft destruction. As part of the alloresponse, monocytes migrate back to the graft and upon leaving the vasculature become inflammatory macrophages or differentiate into dendritic cells and perform additional roles in the graft. Alternately, given appropriate immunosuppression or tolerizing therapies, donor dendritic cells may live for decades throughout a recipient's tissues and contribute to host acceptance of an allograft. Each outcome involves dendritic cell activation, differentiation and migration, in large part as a result of chemokine binding to specific receptors on dendritic cell surface membranes. This review summarizes current research into the roles of chemokines in dendritic cell functions during alloresponses, with an eye toward therapeutic applications. It also considers what must be established if dendritic cells are to be considered by clinicians as realistic targets to circumvent rejection responses.

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Lung transplantation is now considered to be a therapeutic option for patients with end-stage lung diseases. Unfortunately, because the problems of lung allograft rejection, it is only a treatment and not a cure. Critical to the continuum of acute to chronic (bronchiolitis obliterans syndrome) lung allograft rejection is a persistent recruitment of peribronchial/vascular leukocytes, eventually leading to an aberrant reparative process and lung dysfunction. The specific mechanisms by which these leukocytes are recruited to the lung allograft have not been elucidated. Chemokines, through their interactions with specific cell surface receptors, selectively mediate the activation and recruitment of phenotypically distinct cells, a process pivotal to rejection. Multiple studies of human lung rejection and translational studies using animal models have demonstrated “proof of concept” that chemokine ligand/receptor biology plays an important role in pathogenesis of acute rejection and bronchiolitis obliterans syndrome.

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Discerning the mechanisms by which leukocytes gain access to organ allografts is crucial to our understanding of the immunologic basis of organ allograft rejection. Adhesion molecules play prominent roles in all phases of the rejection process. Recent studies have provided detailed insights into the adhesive interactions that guide T cells from the site of activation within secondary lymphoid organs to the graft site. The downstream events, however, by which lymphocytes interact with the functional components of organ allografts, which are predominantly epithelial in origin, are obscure and represent a gap in our understanding of the immunologic basis of allograft rejection. One such interaction involves CD103, a T-cell integrin that recognizes the epithelial cell-specific adhesion molecule, E-cadherin. The focus of this review is to analyze the role of adhesion molecules in lymphocyte trafficking to organ allografts, with specific emphasis on the role of CD103.

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID