Research Topic

Beyond Histocompatibility – Understanding the Non-MHC Determinants Shaping Transplantation Outcome and Tolerance Induction

About this Research Topic

In seventy years, transplantation has progressed from a high-risk experimental procedure, with few transplant recipients surviving into the 2nd year post-transplant, to the standard of care for many end-stage organ diseases. During a similar period of time, the transplantation of allogeneic stem cells ...

In seventy years, transplantation has progressed from a high-risk experimental procedure, with few transplant recipients surviving into the 2nd year post-transplant, to the standard of care for many end-stage organ diseases. During a similar period of time, the transplantation of allogeneic stem cells (AlloHCT) has also become common place for the treatment of malignancy. Much of this success has come from the evolution of immunosuppressants that are able to blunt T cell responses to major and minor histocompatibility antigens that are the dominant T cell targets after transplantation. With these drugs, solid organ transplantation (SOTx) recipients can expect first year survival rates greater than 90%. Many recipients often return to a pre-organ failure lifestyle. With the high success rates in SOTx, we are moving past extending life with transplantation and are now attempting to improve the quality of life of transplant recipients life through the restoration of lost limbs and faces.

In spite of all this success, there are plenty of hurdles to overcome in Transplant Medicine. The toxicities associated T cell targeting immunosuppressants are well appreciated. Yet we lack any viable alternatives to stop the pathology caused by T cells recognizing histocompatibility differences. Furthermore, while immunosuppression is understood as a necessary evil after life-saving solid organ or AlloHCT procedures, it is emerging as a road block for progress in the clinical application of composite tissue allografts (CTA). Here, the side effects of the high doses of immunosuppression needed to prevent rejection after a face or hand transplant may outweigh the benefits provided in life quality for the recipient. While the combination of donor AlloHCT and SOTx has provided evidence that tolerance to donor antigens can be induced, there are unidentified barriers that still stand in the way of the routine induction and durable tolerance.

This Research Topic will aim to encompass Reviews and Original Research articles from transplant researchers seeking to gain an understanding of the mechanisms controlling transplant outcomes or tolerance development and persistence that do not arise from genetic difference between the recipient and donor.

We welcome the submission of articles on the following sub-topics:

1. The role of the microbiome / virome in transplantation and transplant tolerance / GVHD.
2. The influence of innate immune responses in transplantation.
3. Autoimmunity and the transplant recipient.
4. Moving past signal one: co-stimulation, cytokines, and other regulators of immune cells in transplantation.
5. Auxiliary factors that modulate alloimmune responses after SOTx and AlloHCT.
6. Tissue damage, inflammation resolution, tissue repair in transplantation.
7. The role of metabolism in mediating allogeneic immune responses.

We acknowledge the initiation and support of this Research Topic by the International Union of Immunological Societies (IUIS). We hereby state publicly that the IUIS has had no editorial input in articles included in this Research Topic, thus ensuring that all aspects of this Research Topic are evaluated objectively, unbiased by any specific policy or opinion of the IUIS.


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

15 November 2019 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

15 November 2019 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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