Organ allocation for transplantation aims to balance the principles of justice and medical utility to optimally utilize a scarce resource. To address practical considerations, the United States is divided into 58 donor service areas (DSA), each constituting the first unit of allocation. In November 2017, in response to a lawsuit in New York, an emergency action change to lung allocation policy replaced the DSA level of allocation for donor lungs with a 250 nautical mile circle around the donor hospital. Similar policy changes are being implemented for other organs including heart and liver. Findings from a recent US Department of Health and Human Services report, supplemented with data from our institution, suggest that the emergency policy has not resulted in a change in the type of patients undergoing lung transplantation (LT) or early postoperative outcomes. However, there has been a significant decline in local LT, where donor and recipient are in the same DSA. With procurement teams having to travel greater distances, organ ischemic time has increased and median organ cost has more than doubled. We propose potential solutions for consideration at this critical juncture in the field of transplantation. Policymakers should choose equitable and sustainable access for this lifesaving discipline.
| INTRODUC TI ONBronchus-associated lymphoid tissue (BALT) is a pulmonary tertiary lymphoid organ (TLO) that plays a critical role in the inflammatory response to a range of lung pathology, including infection, autoimmunity, and allograft rejection. 1-3 However, recent evidence has emerged that pulmonary TLOs are not synonymous with the generation of deleterious proinflammatory responses. [4][5][6][7] To this end, the development of BALT has been associated with the downregulation of immune responses. Tumor-associated TLOs are one such example, which have been found in both human and mouse models of lung cancer. 4 Pulmonary tumor-associated TLOs are enriched in Foxp3 + regulatory T contributed equally to this manuscript and share first authorship Abbreviations: AHR, aryl hydrocarbon receptor; BALT, bronchus-associated lymphoid tissue; H&E, hematoxylin and eosin; HEV, high endothelial venule; ILC, innate lymphoid cell; NALT, nasal-associated lymphoid tissue; PNAd, peripheral nodal addressin; RORγt, retinoic acid receptor-related orphan receptor gamma t; SLO, secondary lymphoid organ; TLO, tertiary lymphoid organ; γδ, gamma-delta. Long-term survival after lung transplantation remains profoundly limited by graft rejection. Recent work has shown that bronchus-associated lymphoid tissue (BALT), characterized by the development of peripheral nodal addressin (PNAd)-expressing high endothelial venules and enriched in B and Foxp3 + T cells, is important for the maintenance of allograft tolerance. Mechanisms underlying BALT induction in tolerant pulmonary allografts, however, remain poorly understood. Here, we show that the development of PNAd-expressing high endothelial venules within intragraft lymphoid follicles and the recruitment of B cells, but not Foxp3 + cells depends on IL-22. We identify graft-infiltrating gamma-delta (γδ) T cells and Type 3 innate lymphoid cells (ILC3s) as important producers of IL-22. Reconstitution of IL-22 at late time points through retransplantation into wildtype hosts mediates B cell recruitment into lymphoid follicles within the allograft, resulting in a significant increase in their size, but does not induce PNAd expression. Our work has identified cellular and molecular requirements for the induction of BALT in pulmonary allografts during tolerance induction and may provide a platform for the development of new therapies for lung transplant patients. K E Y W O R D S animal models: murine, basic (laboratory) research/science, immunobiology, lung transplantation/pulmonology, lymph node, lymphocyte biology, tolerance: experimental
Drug overdoses have tripled in the United States over the last two decades. With the increasing demand for donor organs, one potential consequence of the opioid epidemic may be an increase in suitable donor organs. Unfortunately, organs from donors dying of drug overdose have poorer utilization rates than other groups of brain‐dead donors, largely due to physician and recipient concerns about viral disease transmission. During the study period of 2011 to 2016, drug overdose donors (DODs) account for an increasingly greater proportion of the national donor pool. We show that a novel model of donor care, known as specialized donor care facility (SDCF), is associated with an increase in organ utilization from DODs compared to the conventional model of hospital‐based donor care. This is likely related to the close relationship of the SDCF with the transplant centers, leading to improved communication and highly efficient donor care.
Regulatory T cells (Treg) have proven to be a powerful immunologic force in nearly every organ system and hold therapeutic potential for a wide range of diseases. Insights gained from non‐transplant pathologies, such as infection, cancer, and autoimmunity, are now being translated to the field of solid organ transplantation, particularly for livers and kidneys. Recent insights from animal models of lung transplantation have established that Tregs play a vital role in suppressing rejection and facilitating tolerance of lung allografts, and such discoveries are being validated in human studies and preclinical trials. Given that long‐term outcomes following lung transplantation remain profoundly limited by chronic rejection, Treg therapy holds the potential to significantly improve patient outcomes and should be aggressively investigated.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.