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Fifty Shades of Transplantation Tolerance: Beyond a Binary Tolerant/Non-Tolerant Paradigm

  • Immunology (R Fairchild, Section Editor)
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Abstract

Purpose of Review

It has long been considered that tolerance in a transplant recipient is a binary all-or-none state: either the graft is accepted without immunosuppression identifying the recipient as tolerant, or the recipient rejects the graft and is not tolerant. This tolerance paradigm, however, does not accurately reflect data emerging from animal models and patients and requires revision.

Recent Findings

It is becoming appreciated that there may be different gradations in the quality of transplantation tolerance based on underlying cellular mechanisms of immunological tolerance, and that individuals may enhance the robustness of their state of transplant tolerance by strengthening or combining different cellular mechanisms. Furthermore, evidence suggests that even if tolerance is lost, the loss may be only temporary, and in some circumstances, tolerance can be restored.

Summary

Shifting our focus from an all-or-nothing tolerance paradigm to one with many shades may help us better understand how tolerance operates, and how this state may be tracked and enhanced for better patient outcomes.

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Funding

M.L.M. was funded by American Heart Association predoctoral fellowships (13PRE14550022 and 15PRE22180007), a Cardiovascular Pathophysiology and Biochemistry Training Grant (T32 HL07237), and a Howard Hughes Medical Institute Med-into-Grad Program training grant (56006772). The work was also supported by National Institutes of Health P01AI-97113 to A.S.C. and M.-L.A.

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Authors and Affiliations

  1. Department of Medicine, Section of Rheumatology, University of Chicago, 924 E. 57th St., JFK-R312, Chicago, IL, 60637, USA

    Michelle L. Miller & Maria-Luisa Alegre

  2. Department of Surgery, Section of Transplantation, University of Chicago, 5841 S. Maryland Ave, Chicago, IL, 60637, USA

    Anita S. Chong

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  1. Michelle L. Miller
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Correspondence to Anita S. Chong or Maria-Luisa Alegre.

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Conflict of Interest

Anita Chong and Maria-Luisa declare grants from the National Institutes of Health during the conduct of this study.

Michelle Miller reports grants from National Institutes of Health, the American Heart Association, and the Howard Hughes Medical Institute during the conduct of the study.

Human and Animal Rights and Informed Consent

Reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

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Miller, M.L., Chong, A.S. & Alegre, ML. Fifty Shades of Transplantation Tolerance: Beyond a Binary Tolerant/Non-Tolerant Paradigm. Curr Transpl Rep 4, 262–269 (2017). https://doi.org/10.1007/s40472-017-0166-5

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