Induction of donor-specific tolerance is referred to as “holy grail” in transplantation medicine, as it would circumvent both chronic rejection and increased morbidity and mortality as side effect from unspecific immunosuppression.

Tolerance is assumed to be an active equilibrium between allo/auto-reactive and regulatory immune mechanisms. Numerous tolerance approaches have been developed in preclinical animal studies, however, when translated in the non-human primate (NHP) or human setting, most of them failed. To date mixed chimerism approach, which is co-transplantation of hematopoietic stem cells and solid organ from the same donor, is the only tolerance approach which has been successfully translated into the clinical setting, however, permanent mixed chimerism is not ideal as it implies the risk of Graft-Versus-Host Disease (GVHD).

Tregs as well as other regulatory cell subsets have been recognized as a promising and potent therapeutic tool in transplantation. Pre-clinical studies as well as first clinical trials have shown that adoptive regulatory cell therapy is a promising therapeutic tool in the treatment of autoimmune diseases and in the induction of tolerance in the field of organ transplantation.

While the majority of ongoing clinical trials seems to suggest that tolerance protocols in clinical practice might be available soon, there is only limited data on long-term results and a lot of questions remain open. Here, we like to tackle the most important questions about tolerance mechanisms and their robustness.

A better understanding of intragraft tolerance mediated by regulatory mechanisms might help to prevent chronic rejection and allo-sensitization with the ambitious goal “one transplant for life”.

In this Research Topic we aim to gather the latest findings and insights on tolerance approaches and regulatory mechanisms enabling tolerance towards allografts. We aim to highlight preclinical and clinical achievements and important questions that still remain open.

We particularly welcome authors to submit the following article types: Original Research, Review, Mini Review, Perspective, Clinical Trial, Case Report, exploring, but not limited to, the following sub-topics:

· Non-deletional tolerance mechanisms

· Transient mixed chimerism

· Split tolerance

· Passenger leucocytes

· Tolerogenic cell therapies

· In situ Treg expansion for tolerance induction

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Frontiers in Immunology

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