Maria-Luisa Alegre , Carl Atkinson , Fadi Issa , Anna Valujskikh , Zheng J. Zhang
{"title":"Best practices of heart transplantation in mice","authors":"Maria-Luisa Alegre , Carl Atkinson , Fadi Issa , Anna Valujskikh , Zheng J. Zhang","doi":"10.1016/j.ajt.2025.04.012","DOIUrl":"10.1016/j.ajt.2025.04.012","url":null,"abstract":"<div><div>Heart transplantation<span><span> in mice has served as a reliable in vivo model in transplant research worldwide for more than half a century. It is not only useful for addressing cardiac graft-specific questions but also provides mechanistic insights and therapeutic strategies that have a broad impact across all solid organ transplants. Compared to other mouse models of </span>solid organ transplantation<span><span>, such as kidney, lung, or small intestine transplants, the surgical techniques to perform mouse heart transplantation (mHT) are relatively easy to master, and the graft heartbeat offers a simple means to evaluate transplant viability. However, as with other in vivo mouse models, mHT has distinct strengths and limitations. Multiple factors can influence the accuracy and reproducibility of the results, including </span>microsurgical techniques and microsurgeons’ skills, postoperative monitoring methodologies, mouse strain combinations, and sex/age. As innovative biotechnologies continue to emerge, the future holds many opportunities for preclinical research utilizing the mHT model. It is therefore imperative to provide the field with optimized mHT protocols and maintain standard reporting requirements. This minireview provided a concise summary and recommendations for standardized practices to ensure the accuracy, reproducibility, and translational value of findings generated from the mHT model.</span></span></div></div>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 9","pages":"Pages 1820-1829"},"PeriodicalIF":8.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Location, location, location—How real estate immunity and preservation of self are defined","authors":"Caitlin Drinkwater, Natasha M. Rogers","doi":"10.1016/j.ajt.2025.07.2473","DOIUrl":"10.1016/j.ajt.2025.07.2473","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 9","pages":"Pages 1810-1811"},"PeriodicalIF":8.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144701086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Active smokers should not be denied access to lung transplantation","authors":"Andrew M. Courtwright","doi":"10.1016/j.ajt.2025.04.022","DOIUrl":"10.1016/j.ajt.2025.04.022","url":null,"abstract":"<div><div><span><span>International society consensus statements, health insurance policies, and individual transplant programs almost uniformly consider active cigarette smoking an absolute contraindication to </span>lung transplant<span><span>. This denial is typically supported on utilitarian grounds—active smokers are prohibitively high-risk because of anticipated poor long-term survival—or nonutilitarian grounds related to fairness in resource allocation to smokers. However, the available literature on </span>lung transplant recipients who resume smoking posttransplant does not demonstrate increased mortality. At the same time, other conditions that carry significant short and long-term posttransplant mortality, such as </span></span>retransplantation<span><span>, are considered relative contraindications. I also suggest that arguments regarding responsibility and fairness do not support the exclusion of active smokers. Patients with lung disease from other ongoing inhalational exposures, including avian antigens in chronic </span>hypersensitivity pneumonitis<span>, are not automatically excluded from transplant. I argue that active smokers are stigmatized, leading smoking to be treated as an inappropriate proxy for nonadherence. I suggest that the lung transplant community should treat active smoking as a relative, not absolute, contraindication to transplant. Transplant program policy should be revised to improve access for active smokers, particularly those who are in urgent need of a transplant and who will not survive long enough to demonstrate smoking abstinence.</span></span></div></div>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 9","pages":"Pages 1851-1857"},"PeriodicalIF":8.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joel S. Freibaum, Riley P. Leathem, William Braaton, Scott M. Krummey
{"title":"Unraveling CD8+ T cell alloimmunity: Insights into the direct pathway of antigen recognition from modern experimental tools","authors":"Joel S. Freibaum, Riley P. Leathem, William Braaton, Scott M. Krummey","doi":"10.1016/j.ajt.2025.05.009","DOIUrl":"10.1016/j.ajt.2025.05.009","url":null,"abstract":"<div><div><span>Early experimental investigations of alloimmunity<span><span> demonstrated that the T cell response against </span>allogeneic antigens is robust and results from a high precursor frequency of responding clones. Seminal studies using cell culture-based methods led to an overall model in which CD8</span></span><sup>+</sup><span><span> T cells can recognize self-peptide complexed to an allogeneic peptide major histocompatibility complex (MHC), termed the direct allogeneic </span>antigen recognition pathway. Recently, 3 groups used modern experimental approaches, including MHC class I tetramers, to further investigate the nature of direct allogeneic antigen recognition by CD8</span><sup>+</sup><span> T cells in mice and humans. In a model of liver-induced transplant tolerance, researchers showed that the MHC class I alloimmune CD8</span><sup>+</sup> T cell response is peptide-dependent. Researchers elucidated the H-L<sup>d</sup> QL9 allogeneic epitope and showed that reactive CD8<sup>+</sup> T cells were peptide discriminating. Researchers also engineered artificial antigen-presenting cells to show that human alloreactive CD8<sup>+</sup><span> T cells against HLA A antigens were MHC restricted and demonstrated a public HLA A2 CD8</span><sup>+</sup> T cell response in 4 donors. Through new experimental tools, these studies offer granular evidence of the mechanisms by which CD8<sup>+</sup> T cells recognize allogeneic antigens and provide a framework for future approaches to selectively target them.</div></div>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 9","pages":"Pages 1843-1850"},"PeriodicalIF":8.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Continued optimism for the use of imlifidase for desensitization in kidney transplant","authors":"Stanley C. Jordan","doi":"10.1016/j.ajt.2025.05.035","DOIUrl":"10.1016/j.ajt.2025.05.035","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 9","pages":"Pages 2028-2029"},"PeriodicalIF":8.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anne M. Halpin , Cathi Murphey , Bruce Motyka , Caishun Li , Jean Pearcey , Maria Ellis , I. Esme Dijke , Simon Urschel , Adam Bingaman , Tess Van Ong , Matthias Kapturczak , Todd L. Lowary , Christopher W. Cairo , Lori J. West
{"title":"Multiplex bead immunoassay in ABO-A2-incompatible kidney transplantation","authors":"Anne M. Halpin , Cathi Murphey , Bruce Motyka , Caishun Li , Jean Pearcey , Maria Ellis , I. Esme Dijke , Simon Urschel , Adam Bingaman , Tess Van Ong , Matthias Kapturczak , Todd L. Lowary , Christopher W. Cairo , Lori J. West","doi":"10.1016/j.ajt.2025.04.003","DOIUrl":"10.1016/j.ajt.2025.04.003","url":null,"abstract":"<div><div>Kidney transplantation from ABO-A2 donors into ABO-O and ABO-B recipients can alleviate inequitable transplant access created by ABO demographics. ABO-A2-incompatible (ABO-A2i) eligibility is determined by anti-A hemagglutination titers. However, titers do not distinguish antibodies specific for A-II glycans, the sole A-antigen subtype in vascular endothelium, from other anti-A antibodies. We examined whether reliance on anti-A titers unnecessarily limited ABO-A2i transplants for candidates with low anti-A-II levels. We created a single-antigen bead immunoassay for ABO antibodies, confirmed the specificity and reproducibility, and demonstrated the ability to detect anti-A and anti-B glycan subtype-specific antibodies in healthy control sera. We then measured subtype-specific anti-A antibodies in original sera from ABO-B and ABO-O candidates who had been previously evaluated for ABO-A2i eligibility. Anti-A-II levels in candidates who had been deemed ineligible (anti-A titers >4) were compared to eligible candidates (anti-A titers ≤4) who had subsequently received ABO-A2i kidneys. Of 141 candidates, 75 (53%) were ineligible; 66 (47%) were eligible and received ABO-A2 kidneys. Retesting original sera, 55% (41/75) of ineligible candidates had anti-A-II levels comparable to eligible candidates. Anti-A titers did not reflect anti-A-II levels. Our ABO antibody assay reproducibly measures graft-specific anti-A-II antibodies, providing information beyond anti-A titers that may increase transplant access for ABO-B and ABO-O candidates.</div></div>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 9","pages":"Pages 1884-1894"},"PeriodicalIF":8.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Managing the logistics of the new allocation policies","authors":"By Lara C. Pullen","doi":"10.1016/j.ajt.2025.07.2465","DOIUrl":"10.1016/j.ajt.2025.07.2465","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 9","pages":"Pages 1807-1809"},"PeriodicalIF":8.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144701087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A closer examination of the ethical principles when considering active smokers as candidates for lung transplant","authors":"Alyssa A. Perez, Lorriana E. Leard","doi":"10.1016/j.ajt.2025.06.020","DOIUrl":"10.1016/j.ajt.2025.06.020","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 9","pages":"Pages 1816-1817"},"PeriodicalIF":8.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah J. Colpitts , Sinthuja Jegatheeswaran , Amanda Oakie , Siavash Mashhouri , Nadia Sachewsky , Humaira Murshed , Jessica A. Mathews , Kyle T. Reid , Paraish S. Misra , Vivian C.W. Fung , Trevor W. Reichman , M. Cristina Nostro , C.Bruce Verchere , Megan K. Levings , Sarah Q. Crome
{"title":"Cell therapy with human interleukin 10–producing ILC2s enhances islet function and inhibits allograft rejection","authors":"Sarah J. Colpitts , Sinthuja Jegatheeswaran , Amanda Oakie , Siavash Mashhouri , Nadia Sachewsky , Humaira Murshed , Jessica A. Mathews , Kyle T. Reid , Paraish S. Misra , Vivian C.W. Fung , Trevor W. Reichman , M. Cristina Nostro , C.Bruce Verchere , Megan K. Levings , Sarah Q. Crome","doi":"10.1016/j.ajt.2025.05.023","DOIUrl":"10.1016/j.ajt.2025.05.023","url":null,"abstract":"<div><div>Group 2 innate lymphoid cells (ILC2s) that produce interleukin (IL)-10 (IL-10<sup>+</sup>ILC2s) have demonstrated regulatory and tissue-protective properties in murine studies, but preclinical studies are lacking that explore the potential of human IL-10<sup>+</sup>ILC2s as a tolerance-promoting cell therapy for transplantation or autoimmunity. Here, we investigated whether human IL-10<sup>+</sup>ILC2s could enhance islet function and prevent allograft rejection in humanized mouse models of islet transplantation. <em>In vitro</em>, human IL-10<sup>+</sup>ILC2s did not display cytotoxicity toward allogeneic deceased-donor islets or stem cell–derived islet-like cells, and co-transplantation with IL-10<sup>+</sup>ILC2s significantly improved glucose control post-transplantation. Allogeneic IL10<sup>+</sup>ILC2s directly inhibited T cell–mediated cytotoxicity against islet-like cells <em>in vitro</em> and, in an antigen-specific transplant rejection model, prevented T cell–mediated rejection of deceased-donor islet grafts. Effects were greater with allogeneic IL-10<sup>+</sup>ILC2s, as autologous cells did not inhibit T cell interferon-γ production or cytotoxic activity <em>in vitro</em> and were not sufficient to prevent islet rejection <em>in vivo</em>. Collectively, these studies provide proof-of-principle that human IL-10<sup>+</sup>ILC2s have therapeutic potential for islet transplantation and type 1 diabetes and support their use as an allogeneic regulatory cell therapy.</div></div>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 9","pages":"Pages 1858-1869"},"PeriodicalIF":8.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brendan P. Lovasik, Jessica Lindemann, William C. Chapman
{"title":"Fever, cytopenia, and splenomegaly in a liver transplant patient","authors":"Brendan P. Lovasik, Jessica Lindemann, William C. Chapman","doi":"10.1016/j.ajt.2025.03.032","DOIUrl":"10.1016/j.ajt.2025.03.032","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 9","pages":"Pages 2023-2025"},"PeriodicalIF":8.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}