Spontaneous restoration of transplantation tolerance after acute rejection

Michelle L. Miller, Melvin D. Daniels, Tongmin Wang, Jianjun Chen, James Young, Jing Xu, Ying Wang, Dengping Yin, Vinh Vu, Aliya N. Husain, Maria-Luisa Alegre () and Anita S. Chong ()
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Michelle L. Miller: Section of Rheumatology, The University of Chicago
Melvin D. Daniels: Section of Transplantation, The University of Chicago
Tongmin Wang: Section of Transplantation, The University of Chicago
Jianjun Chen: Section of Transplantation, The University of Chicago
James Young: Section of Transplantation, The University of Chicago
Jing Xu: Section of Transplantation, The University of Chicago
Ying Wang: Section of Rheumatology, The University of Chicago
Dengping Yin: Section of Transplantation, The University of Chicago
Vinh Vu: Section of Transplantation, The University of Chicago
Aliya N. Husain: University of Chicago, The University of Chicago
Maria-Luisa Alegre: Section of Rheumatology, The University of Chicago
Anita S. Chong: Section of Transplantation, The University of Chicago

Nature Communications, 2015, vol. 6, issue 1, 1-9

Abstract: Abstract Transplantation is a cure for end-stage organ failure but, in the absence of pharmacological immunosuppression, allogeneic organs are acutely rejected. Such rejection invariably results in allosensitization and accelerated rejection of secondary donor-matched grafts. Transplantation tolerance can be induced in animals and a subset of humans, and enables long-term acceptance of allografts without maintenance immunosuppression. However, graft rejection can occur long after a state of transplantation tolerance has been acquired. When such an allograft is rejected, it has been assumed that the same rules of allosensitization apply as to non-tolerant hosts and that immunological tolerance is permanently lost. Using a mouse model of cardiac transplantation, we show that when Listeria monocytogenes infection precipitates acute rejection, thus abrogating transplantation tolerance, the donor-specific tolerant state re-emerges, allowing spontaneous acceptance of a donor-matched second transplant. These data demonstrate a setting in which the memory of allograft tolerance dominates over the memory of transplant rejection.

Date: 2015
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DOI: 10.1038/ncomms8566

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