TY - JOUR
T1 - Tolerance is the achievable 'Holy Grail' in transplantation
AU - Yuan, Xueli
AU - Ansari, Mohammed Javeed
AU - Sayegh, Mohamed H.
PY - 2006/2
Y1 - 2006/2
N2 - Purpose of review: Despite great progress in organ transplantation, long-term outcomes are far from satisfactory and induction of tolerance remains the 'Holy Grail' for transplant clinicians. Although challenges remain, recent developments in our understanding of the mechanisms of tolerance in animal models and humans have moved us closer to the ultimate goal of achieving clinical transplantation tolerance in humans. This review highlights the newest developments in the quest to achieve such a state. Recent findings: Both deletional and nondeletional mechanisms, achieved by a variety of strategies, are involved in tolerance induction. Regulation carried out by Foxp3 expressing CD25+CD4+ regulatory T (Treg) cells is considered one of the most important nondeletional mechanisms of tolerance. Tolerance can be achieved and maintained by manipulating costimulatory signals, which closely influence the function of Treg cells. Summary: A variety of depletional and nondepletional strategies targeting the T cells, B cells, dendritic cells, and natural killer cells have all been shown to be important in the development and function of Treg cells. T reg cell therapy holds great promise for revolutionizing the field of transplantation. A vast body of experimental data exists indicating that tolerance can be now achieved; the challenge, however, rests in translating this success to the clinic.
AB - Purpose of review: Despite great progress in organ transplantation, long-term outcomes are far from satisfactory and induction of tolerance remains the 'Holy Grail' for transplant clinicians. Although challenges remain, recent developments in our understanding of the mechanisms of tolerance in animal models and humans have moved us closer to the ultimate goal of achieving clinical transplantation tolerance in humans. This review highlights the newest developments in the quest to achieve such a state. Recent findings: Both deletional and nondeletional mechanisms, achieved by a variety of strategies, are involved in tolerance induction. Regulation carried out by Foxp3 expressing CD25+CD4+ regulatory T (Treg) cells is considered one of the most important nondeletional mechanisms of tolerance. Tolerance can be achieved and maintained by manipulating costimulatory signals, which closely influence the function of Treg cells. Summary: A variety of depletional and nondepletional strategies targeting the T cells, B cells, dendritic cells, and natural killer cells have all been shown to be important in the development and function of Treg cells. T reg cell therapy holds great promise for revolutionizing the field of transplantation. A vast body of experimental data exists indicating that tolerance can be now achieved; the challenge, however, rests in translating this success to the clinic.
KW - Costimulation
KW - Regulation
KW - T cell
KW - Tolerance
KW - Transplantation
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U2 - 10.1097/01.mot.0000203880.02687.18
DO - 10.1097/01.mot.0000203880.02687.18
M3 - Review article
AN - SCOPUS:33644627727
SN - 1087-2418
VL - 11
SP - 24
EP - 29
JO - Current opinion in organ transplantation
JF - Current opinion in organ transplantation
IS - 1
ER -