title: 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.affiliation: Section of Rheumatology, Department of Medicine, The University of Chicago, 924 E. 57th Street, JFK-R302, Chicago, Illinois 60637, USA.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Miller
authors.affiliation: Section of Transplantation, Department of Surgery, The University of Chicago, 5841 S. Maryland Avenue, Chicago, Illinois 60637, USA.|Department of Biological Sciences, Chicago State University, 9501 S. King Drive, Chicago, Illinois 60628, USA.
authors.forename: Melvin D
authors.initials: MD
authors.lastname: Daniels
authors.affiliation: Section of Transplantation, Department of Surgery, The University of Chicago, 5841 S. Maryland Avenue, Chicago, Illinois 60637, USA.
authors.forename: Tongmin
authors.initials: T
authors.lastname: Wang
authors.affiliation: Section of Transplantation, Department of Surgery, The University of Chicago, 5841 S. Maryland Avenue, Chicago, Illinois 60637, USA.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Section of Transplantation, Department of Surgery, The University of Chicago, 5841 S. Maryland Avenue, Chicago, Illinois 60637, USA.
authors.forename: James
authors.initials: J
authors.lastname: Young
authors.affiliation: Section of Transplantation, Department of Surgery, The University of Chicago, 5841 S. Maryland Avenue, Chicago, Illinois 60637, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Section of Rheumatology, Department of Medicine, The University of Chicago, 924 E. 57th Street, JFK-R302, Chicago, Illinois 60637, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Section of Transplantation, Department of Surgery, The University of Chicago, 5841 S. Maryland Avenue, Chicago, Illinois 60637, USA.
authors.forename: Dengping
authors.initials: D
authors.lastname: Yin
authors.affiliation: Section of Transplantation, Department of Surgery, The University of Chicago, 5841 S. Maryland Avenue, Chicago, Illinois 60637, USA.
authors.forename: Vinh
authors.initials: V
authors.lastname: Vu
authors.affiliation: Department of Pathology, University of Chicago, The University of Chicago, 5841 S. Maryland Avenue, Chicago, Illinois 60637, USA.
authors.forename: Aliya N
authors.initials: AN
authors.lastname: Husain
authors.affiliation: Section of Rheumatology, Department of Medicine, The University of Chicago, 924 E. 57th Street, JFK-R302, Chicago, Illinois 60637, USA.
authors.forename: Maria-Luisa
authors.initials: ML
authors.lastname: Alegre
authors.affiliation: Section of Transplantation, Department of Surgery, The University of Chicago, 5841 S. Maryland Avenue, Chicago, Illinois 60637, USA.
authors.forename: Anita S
authors.initials: AS
authors.lastname: Chong
mesh_terms: D000818:Animals; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D016027:Heart Transplantation / Q000009:adverse effects*; D007108:Immune Tolerance; D008089:Listeria monocytogenes; D008088:Listeriosis / Q000150:complications / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D023001:Transplantation Tolerance / Q000276:immunology