Current status of clinical transplantation tolerance

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Purpose of review

The purpose of this review is to discuss a recent shift of attitude regarding immunosuppression for solid organ transplants. A culture of increasing immunosuppression and incorporating new and powerful agents into an already effective regimen has resulted in overimmunosuppression and an increased incidence of sepsis without an improvement in long-term functional graft survival.

Recent findings

Overimmunosuppression is probably detrimental in another and important way. Increasing evidence points to natural control and ‘switching off’ of the immune response as an active and vital function of the immune system. Excessive immunosuppression is therefore likely to prevent the development of natural tolerance or operational tolerance mechanisms.


The implication of this important psychological change in attitude to immunosuppression is for minimal immunosuppression to allow for regulatory mechanisms to develop naturally. These strategies are likely to influence prescribing for individual patients because of the marked polymorphism of the main HLA system and the variation of individual potential in the immune response. To this end alemtuzumab (Campath 1H) in one or two doses at the time of transplantation followed by low-dose monotherapy with a calcineurin inhibitor would appear to be a step in the direction of almost or prope tolerance.

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