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Cross-immune tolerance-project

Cross-immune tolerance-project - Cellular Molecular...

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REVIEW Cross-immune tolerance: conception and its potential significance on transplantation tolerance Yong Zhao 1 and Xianchang Li 2 The diversity of alloreactive T cells in graft rejection and the presence of extensive crossreactivity among alloreactive T cells indicate that the induction of transplantation tolerance may fundamentally alter the size of host T-cell repertoire involved in protective immunity and immune surveillance, especially those that are crossreactive to conventional antigens. We herein highlight the crossreactive nature of alloreactive T cells and the potential risks of altered T-cell repertoire associated with the induction of transplantation tolerance. The possibility that T-cell tolerance to one set of antigens results in their tolerance to other unrelated antigens due to T-cell crossreactivity and/or heterogeneity is defined as ‘cross-immune tolerance’. The definition and significance of this concept were discussed in details. Cellular & Molecular Immunology (2010) 7, 20–25; doi:10.1038/cmi.2009.101; published online 23 December 2009 Keywords: crossreactivity; T-cell repertoire; tolerance; transplantation INTRODUCTION Induction of transplantation tolerance in the clinic without the needs for chronic immunosuppression remains the ultimate goal in trans- plantation research. Tolerance in transplant models is traditionally defined as permanent acceptance of donor organs following a period of inductive therapy, but the host immune response to other antigens is preserved. Multiple mechanisms including T-cell deletion, anergy and active immune regulation collectively contribute to the induction and maintenance of transplantation tolerance. It is well known that the frequency of T cells that respond to transplant antigens is remarkably high, 1,2 and such high responder frequency constitutes one of the potent barriers to the induction of transplantation tolerance. 3 We now know that the alloreactive T-cell repertoire involved in transplant rejection is far more complex and diverse than initially anticipated. Besides T cells that are intrinsically reactive to alloantigens, a consid- erable fraction of T cells that are programmed to respond to nominal antigens can also be crossreactive to alloantigens. 4–6 Importantly, recent studies have convincingly demonstrated that certain memory T cells that are specific to conventional pathogens are highly alloreac- tive in transplant models. 3 The crossreactive nature of alloreactive T cells clearly highlights the flexibility of T-cell receptors (TCR) in their recognition of transplant antigens. In fact, such TCR flexibility is not unique to transplant models and may represent a general feature of T- cell recognition of a wide variety of antigenic epitopes.
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