Spontaneous restoration of transplantation tolerance after acute rejection.

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.

• Authors: 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, Anita S Chong
• Journal: Nature communications (Nat Commun) Vol. 6 Pg. 7566 (Jul 07 2015) ISSN: 2041-1723 [Electronic] England
• PMID: 26151823 (Publication Type: Journal Article, Research Support, American Recovery and Reinvestment Act, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Topics

• Animals
• Female
• Graft Rejection
• Graft Survival
• Heart Transplantation (adverse effects)
• Immune Tolerance
• Listeria monocytogenes
• Listeriosis (complications, immunology)
• Mice
• Mice, Inbred Strains
• Transplantation Tolerance (immunology)