{"title":"Corrigendum to \"Outcomes and motivations in unspecified (nondirected altruistic) kidney donation: Results from a United Kingdom prospective cohort study\" [American Journal of Transplantation. Volume 25, Issue 9, September 2025, Pages 1965-1975].","authors":"Hannah Maple,Petrut Gogalniceanu,Mira Zuchowski,Heather Draper,Lisa Burnapp,Paul McCrone,Joseph Chilcot,Sam Norton,Nizam Mamode","doi":"10.1016/j.ajt.2026.03.004","DOIUrl":"https://doi.org/10.1016/j.ajt.2026.03.004","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"13 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147493068","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}
Pub Date : 2026-03-19DOI: 10.1016/j.ajt.2026.01.031
Macey L Levan,Dorry L Segev,Allan B Massie
{"title":"Reply to \"Disparities through the looking glass\".","authors":"Macey L Levan,Dorry L Segev,Allan B Massie","doi":"10.1016/j.ajt.2026.01.031","DOIUrl":"https://doi.org/10.1016/j.ajt.2026.01.031","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"30 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147493069","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}
Pub Date : 2026-03-16DOI: 10.1016/j.ajt.2026.03.007
Davide Schiliró, Matt Tunbridge, Nolan J. Brown, Joshua Lopez, Tammy Tollison, Ethan Smith, Joseph Ladowski, Alessandro Martinino, Meghan Hu, Allison Schwalb, Janghoon Yoon, Rafaela Belloni, John J. O’Neil, Luke N. Robinson, Asher D. Schachter, Gregory J. Babcock, David Oldach, Xinxia Peng, H. Kay Chung, Stuart Knechtle, Jean Kwun
The interleukin-2 mutein, VIS171, was engineered to extend half-life and enhance selective binding and expansion of regulatory T cells (Tregs) expressing high levels of the trimeric IL-2 receptor (IL-2R). Our study evaluated the effects of VIS171 on immune cell populations in nonhuman primates, focusing on its ability to selectively expand Tregs and characterize their phenotype during expansion and contraction. Naïve rhesus macaques were treated with VIS171 subcutaneously, along with daily rapamycin. VIS171 was well tolerated with repeated administration. Tregs, identified as CD4+CD25+FoxP3+ or CD4+CD25+CD127lo cells, expanded significantly after treatment. Peak Treg expansion was evident in the peripheral circulation between days 5 and 7 post-dose, with frequency and absolute counts markedly increasing between 4- and 6-fold after administration. In contrast, no significant effect was shown on cytotoxic T lymphocytes (CTLs) populations, highlighting the specificity for expanding Tregs. Single-cell RNA sequencing revealed three distinct Treg clusters: resting (SELLhigh) and two subsets with distinct activation and metabolic profiles, (HACD4high and TIGIThigh). The transcriptomic profile of expanded Tregs showed consistent with an effector Treg signature associated with immunoregulatory function. Differentiation signature scores indicated preserved Treg functionality following expansion. These findings suggest that VIS171 with rapamycin promotes robust, selective, and durable Treg expansion, offering a strategy to enhance transplant tolerance without broad immunosuppression.
{"title":"Selective Impact on Regulatory T cell with Sustained Functional Phenotype by the IL-2 Mutein VIS171 in a Nonhuman Primate Model","authors":"Davide Schiliró, Matt Tunbridge, Nolan J. Brown, Joshua Lopez, Tammy Tollison, Ethan Smith, Joseph Ladowski, Alessandro Martinino, Meghan Hu, Allison Schwalb, Janghoon Yoon, Rafaela Belloni, John J. O’Neil, Luke N. Robinson, Asher D. Schachter, Gregory J. Babcock, David Oldach, Xinxia Peng, H. Kay Chung, Stuart Knechtle, Jean Kwun","doi":"10.1016/j.ajt.2026.03.007","DOIUrl":"https://doi.org/10.1016/j.ajt.2026.03.007","url":null,"abstract":"The interleukin-2 mutein, VIS171, was engineered to extend half-life and enhance selective binding and expansion of regulatory T cells (Tregs) expressing high levels of the trimeric IL-2 receptor (IL-2R). Our study evaluated the effects of VIS171 on immune cell populations in nonhuman primates, focusing on its ability to selectively expand Tregs and characterize their phenotype during expansion and contraction. Naïve rhesus macaques were treated with VIS171 subcutaneously, along with daily rapamycin. VIS171 was well tolerated with repeated administration. Tregs, identified as CD4<ce:sup loc=\"post\">+</ce:sup>CD25<ce:sup loc=\"post\">+</ce:sup>FoxP3<ce:sup loc=\"post\">+</ce:sup> or CD4<ce:sup loc=\"post\">+</ce:sup>CD25<ce:sup loc=\"post\">+</ce:sup>CD127<ce:sup loc=\"post\">lo</ce:sup> cells, expanded significantly after treatment. Peak Treg expansion was evident in the peripheral circulation between days 5 and 7 post-dose, with frequency and absolute counts markedly increasing between 4- and 6-fold after administration. In contrast, no significant effect was shown on cytotoxic T lymphocytes (CTLs) populations, highlighting the specificity for expanding Tregs. Single-cell RNA sequencing revealed three distinct Treg clusters: resting (<ce:italic>SELL</ce:italic><ce:sup loc=\"post\">high</ce:sup>) and two subsets with distinct activation and metabolic profiles, (HACD4<ce:sup loc=\"post\">high</ce:sup> and TIGIT<ce:sup loc=\"post\">high</ce:sup>). The transcriptomic profile of expanded Tregs showed consistent with an effector Treg signature associated with immunoregulatory function. Differentiation signature scores indicated preserved Treg functionality following expansion. These findings suggest that VIS171 with rapamycin promotes robust, selective, and durable Treg expansion, offering a strategy to enhance transplant tolerance without broad immunosuppression.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"4 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147465792","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}
Pub Date : 2026-03-16DOI: 10.1016/j.ajt.2026.03.010
Brendan P. Lovasik MD, Cristin Garrett MD, Rebecca Zhang MS, Mengyu Di MS, Raymond J. Lynch MD, Rachel E. Patzer PhD MPH, Andrew B. Adams MD PhD
The number of patients with a failed kidney transplant who are being considered for retransplantation is increasing steadily. However, disparities in access to repeat waitlisting and retransplant have not been well described. We examined a cohort of 102,891 patients with a failed kidney transplant in the United States Renal Data System (1995-2022), and assessed access to repeat wait-listing and repeat transplantation. Approximately half of the study population was re-listed after graft failure, including similar proportions of white (49.6%), and Black (46.8%), and Hispanic patients (49.9%). There were no differences in re-waitlisting of either Black (HR 1.00, 95% CI 0.97-1.02) or Hispanic (HR 1.01, 95% CI 0.98-1.04) patients regardless of sociodemographics or clinical covariables, Interestingly, White patients had a higher rate of retransplantation (30.9%) than Black (20.8%; HR 0.67, 95% CI 0.65-0.69) or Hispanic (26.8%; HR 0.78; 95% CI 0.75-0.81) patients when sociodemographics or clinical covariables were controlled. When stratified by recipient PRA, racial disparities were reduced; however, moderate and highly sensitized Black and Hispanic patients had reduced access to retransplant from the waiting list. Access to the waitlist alone does not account for racial/ethnic differences in retransplantation; policies and strategies addressing both sociodemographic and immunologic disparities should be promoted to improve access to kidney retransplant for minority patients.
肾移植失败后考虑再次移植的患者数量正在稳步增加。然而，在获得重复等候名单和重新移植方面的差异并没有得到很好的描述。我们研究了美国肾脏数据系统（1995-2022）中102,891例肾移植失败患者的队列，并评估了重复等待名单和重复移植的可及性。大约一半的研究人群在移植物失败后重新入选，包括相似比例的白人（49.6%）、黑人（46.8%）和西班牙裔患者（49.9%）。无论社会人口统计学或临床变量如何，黑人（HR 1.00, 95% CI 0.97-1.02）或西班牙裔（HR 1.01, 95% CI 0.98-1.04）患者的重新等待名单均无差异。有趣的是，在控制社会人口统计学或临床变量后，白人患者的再移植率（30.9%）高于黑人（20.8%,HR 0.67, 95% CI 0.65-0.69）或西班牙裔（26.8%,HR 0.78, 95% CI 0.75-0.81）患者。当按接受者PRA分层时，种族差异减小；然而，中等和高度敏感的黑人和西班牙裔患者从等待名单中获得再次移植的机会减少。获得候补名单本身并不能解释再移植的种族/民族差异；应促进解决社会人口统计学和免疫差异的政策和战略，以改善少数民族患者获得肾脏再移植的机会。
{"title":"Racial and Immunologic Disparities Impact Access to Kidney Re-Waitlisting and Retransplantation","authors":"Brendan P. Lovasik MD, Cristin Garrett MD, Rebecca Zhang MS, Mengyu Di MS, Raymond J. Lynch MD, Rachel E. Patzer PhD MPH, Andrew B. Adams MD PhD","doi":"10.1016/j.ajt.2026.03.010","DOIUrl":"https://doi.org/10.1016/j.ajt.2026.03.010","url":null,"abstract":"The number of patients with a failed kidney transplant who are being considered for retransplantation is increasing steadily. However, disparities in access to repeat waitlisting and retransplant have not been well described<ce:italic>.</ce:italic> We examined a cohort of 102,891 patients with a failed kidney transplant in the United States Renal Data System (1995-2022), and assessed access to repeat wait-listing and repeat transplantation. Approximately half of the study population was re-listed after graft failure, including similar proportions of white (49.6%), and Black (46.8%), and Hispanic patients (49.9%). There were no differences in re-waitlisting of either Black (HR 1.00, 95% CI 0.97-1.02) or Hispanic (HR 1.01, 95% CI 0.98-1.04) patients regardless of sociodemographics or clinical covariables, Interestingly, White patients had a higher rate of retransplantation (30.9%) than Black (20.8%; HR 0.67, 95% CI 0.65-0.69) or Hispanic (26.8%; HR 0.78; 95% CI 0.75-0.81) patients when sociodemographics or clinical covariables were controlled. When stratified by recipient PRA, racial disparities were reduced; however, moderate and highly sensitized Black and Hispanic patients had reduced access to retransplant from the waiting list. Access to the waitlist alone does not account for racial/ethnic differences in retransplantation; policies and strategies addressing both sociodemographic and immunologic disparities should be promoted to improve access to kidney retransplant for minority patients.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"9 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147465789","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}
Pub Date : 2026-03-14DOI: 10.1016/j.ajt.2026.03.011
Avery Wilson,Andre Souffrant,Bryar Hansen,A B Cosimi,David Sachs,Tatsuo Kawai
In current clinical practice, successful kidney transplantation requires life-long immunosuppression to prevent graft rejection, which is unfortunately associated with significant morbidity, mortality, and reduced quality of life. Over the past two decades, there has been growing interest and encouraging progress in clinical therapeutic approaches to transplantation tolerance, defined as stable allograft acceptance in the absence of chronic immunosuppression. To date, these advances have largely been based on the concept of hematopoietic chimerism, achieved by bone marrow or hematopoietic stem cell transplantation performed at the time of solid-organ transplant. Recipients undergo a conditioning regimen prior to combined kidney and bone marrow transplantation that allows donor-derived hematopoietic cells to expand persistently or transiently. These clinical trials were based on foundational concepts developed through a half-century of preclinical work in mice and large animal models. Preclinical models have also proven essential in addressing unforeseen challenges arising through the clinical trials. In this review we will discuss the foundational basic studies in murine models and preclinical work in large animal models and the current clinical efforts to achieve allograft tolerance in kidney transplantation.
{"title":"Preclinical and Clinical Studies on Kidney Allograft Tolerance via Hematopoietic Chimerism.","authors":"Avery Wilson,Andre Souffrant,Bryar Hansen,A B Cosimi,David Sachs,Tatsuo Kawai","doi":"10.1016/j.ajt.2026.03.011","DOIUrl":"https://doi.org/10.1016/j.ajt.2026.03.011","url":null,"abstract":"In current clinical practice, successful kidney transplantation requires life-long immunosuppression to prevent graft rejection, which is unfortunately associated with significant morbidity, mortality, and reduced quality of life. Over the past two decades, there has been growing interest and encouraging progress in clinical therapeutic approaches to transplantation tolerance, defined as stable allograft acceptance in the absence of chronic immunosuppression. To date, these advances have largely been based on the concept of hematopoietic chimerism, achieved by bone marrow or hematopoietic stem cell transplantation performed at the time of solid-organ transplant. Recipients undergo a conditioning regimen prior to combined kidney and bone marrow transplantation that allows donor-derived hematopoietic cells to expand persistently or transiently. These clinical trials were based on foundational concepts developed through a half-century of preclinical work in mice and large animal models. Preclinical models have also proven essential in addressing unforeseen challenges arising through the clinical trials. In this review we will discuss the foundational basic studies in murine models and preclinical work in large animal models and the current clinical efforts to achieve allograft tolerance in kidney transplantation.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"27 20 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147465241","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}
Split liver transplantation addresses organ shortage; however, the outcomes and risk factors full-right/full-left split liver transplantation (FR/FLSLT) require validation using multicenter data. This retrospective multicenter study included 132 FR/FLSLT recipients from five Chinese centers (May 2016-November 2024). Risk factors affecting survival were analyzed, stratified by graft-to-recipient weight ratio (GRWR) and risk factors. The overall 3-year recipient and graft survival rates were 84.1% and 81.8%, respectively. Recipients with a GRWR ≤ 1.15 exhibited significantly lower 3-year survival versus GRWR > 1.15 (58.1% vs. 91.7% recipient survival; 55.3% vs. 89.8% graft survival; P < 0.001). Multivariate analysis identified recipient age > 52 and MELD score > 15 as independent mortality risk factors. In patients without risk factors, no mortality or graft-loss events were observed in the GRWR ≤ 1.15 group, but the small sample size (n = 3) limits the interpretation. However, with ≥ 1 risk factors, a GRWR ≤ 1.15 significantly increased mortality (HR 8.81, P < 0.001) and graft loss (HR 7.50, P < 0.001). FR/FLSLT with GRWR > 1.15 demonstrated favorable outcomes. GRWR ≤ 1.15 grafts may be considered for recipients without identified risk factors (age ≤ 52 , MELD score ≤ 15), and this requires further multicenter validation.
劈裂肝移植解决器官短缺问题；然而，全右/全左分离肝移植（FR/FLSLT）的结果和危险因素需要多中心数据验证。这项回顾性多中心研究包括来自中国五个中心的132名FR/FLSLT患者（2016年5月- 2024年11月）。分析影响生存的危险因素，并按移植物与受体重量比（GRWR）和危险因素进行分层。总的3年受者和移植物存活率分别为84.1%和81.8%。GRWR≤1.15的受体3年生存率明显低于GRWR≤1.15的受体（58.1% vs. 91.7%; 55.3% vs. 89.8%; P < 0.001）。多因素分析确定受体年龄bbbb52和MELD评分b>5为独立死亡危险因素。在没有危险因素的患者中，GRWR≤1.15组未观察到死亡或移植物丢失事件，但样本量小（n = 3）限制了解释。然而，当危险因素≥1时，GRWR≤1.15显著增加死亡率（HR 8.81, P < 0.001）和移植物损失（HR 7.50, P < 0.001）。FR/FLSLT的GRWR为bb0 1.15，结果良好。GRWR≤1.15可以考虑无危险因素（年龄≤52岁，MELD评分≤15）的受者移植，这需要进一步的多中心验证。
{"title":"Determining the Critical Graft-to-recipient Weight Ratio Threshold for Safety in Full-right/Full-left Split Liver Transplantation: A Multicentric Cohort Study.","authors":"Mingzheng Chen,Sui Shen,Zixuan Feng,Shuo Wang,Jan Lerut,Xiao Xu,Zhijun Zhu,Jinzhen Cai,Yang Yang,Shuhong Yi,Guangming Li,Nan Ye,Wu Gu,Xingyu Luo,Kai Wun Chang,Li Zhuang,Peng Liu,Shusen Zheng,Zhe Yang","doi":"10.1016/j.ajt.2026.03.009","DOIUrl":"https://doi.org/10.1016/j.ajt.2026.03.009","url":null,"abstract":"Split liver transplantation addresses organ shortage; however, the outcomes and risk factors full-right/full-left split liver transplantation (FR/FLSLT) require validation using multicenter data. This retrospective multicenter study included 132 FR/FLSLT recipients from five Chinese centers (May 2016-November 2024). Risk factors affecting survival were analyzed, stratified by graft-to-recipient weight ratio (GRWR) and risk factors. The overall 3-year recipient and graft survival rates were 84.1% and 81.8%, respectively. Recipients with a GRWR ≤ 1.15 exhibited significantly lower 3-year survival versus GRWR > 1.15 (58.1% vs. 91.7% recipient survival; 55.3% vs. 89.8% graft survival; P < 0.001). Multivariate analysis identified recipient age > 52 and MELD score > 15 as independent mortality risk factors. In patients without risk factors, no mortality or graft-loss events were observed in the GRWR ≤ 1.15 group, but the small sample size (n = 3) limits the interpretation. However, with ≥ 1 risk factors, a GRWR ≤ 1.15 significantly increased mortality (HR 8.81, P < 0.001) and graft loss (HR 7.50, P < 0.001). FR/FLSLT with GRWR > 1.15 demonstrated favorable outcomes. GRWR ≤ 1.15 grafts may be considered for recipients without identified risk factors (age ≤ 52 , MELD score ≤ 15), and this requires further multicenter validation.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"9 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147454590","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}
In kidney transplantation (KTX), the immune response against the graft is mediated by donor-reactive T-cells (DRTCs). Urine represents a potentially informative but understudied T-cell compartment, particularly during rejection. Here, in a prospective open cohort study recruiting KTX recipients and collecting urine as well as peripheral blood mononuclear cells (PBMCs), we characterized the urinary and circulating T-cell receptor (TCR) repertoires of seven patients with rejection and seven controls, by next-generation sequencing (NGS). DRTC populations were defined via Mixed lymphocyte reactions (MLR) performed with PBMCs collected both pre-transplant and at biopsy. At biopsy, TCR mRNA was found in the urine of all rejectors but only three/seven controls (p=0.035). The urinary repertoires were distinct from the circulating repertoires of the respective patients, with 63±19% (mean ± SD) of urinary clonotypes being unique to this compartment. Further, urinary repertoires were consistently and significantly enriched in DRTCs compared to circulation, in both groups. Defining DRTCs at biopsy allowed identification of previously uncaptured clonotypes. Compared to all DRTC clonotypes, those also detected in urine expanded in circulation at an increased rate, from pre-transplant to the date of biopsy. The higher abundance of DRTCs in urine highlights its potential for monitoring DRTC dynamics following transplantation.
{"title":"Donor-reactive clonotypes are overrepresented in the urinary T-cell repertoire during kidney transplant rejection and show distinct dynamics in the circulation.","authors":"Constantin Aschauer,Andreas Heinzel,Karin Hu,Hao Shan Chen,Roman Reindl-Schwaighofer,Thomas Wekerle,Megan Sykes,Ana Filipa David,Rainer Oberbauer","doi":"10.1016/j.ajt.2026.03.008","DOIUrl":"https://doi.org/10.1016/j.ajt.2026.03.008","url":null,"abstract":"In kidney transplantation (KTX), the immune response against the graft is mediated by donor-reactive T-cells (DRTCs). Urine represents a potentially informative but understudied T-cell compartment, particularly during rejection. Here, in a prospective open cohort study recruiting KTX recipients and collecting urine as well as peripheral blood mononuclear cells (PBMCs), we characterized the urinary and circulating T-cell receptor (TCR) repertoires of seven patients with rejection and seven controls, by next-generation sequencing (NGS). DRTC populations were defined via Mixed lymphocyte reactions (MLR) performed with PBMCs collected both pre-transplant and at biopsy. At biopsy, TCR mRNA was found in the urine of all rejectors but only three/seven controls (p=0.035). The urinary repertoires were distinct from the circulating repertoires of the respective patients, with 63±19% (mean ± SD) of urinary clonotypes being unique to this compartment. Further, urinary repertoires were consistently and significantly enriched in DRTCs compared to circulation, in both groups. Defining DRTCs at biopsy allowed identification of previously uncaptured clonotypes. Compared to all DRTC clonotypes, those also detected in urine expanded in circulation at an increased rate, from pre-transplant to the date of biopsy. The higher abundance of DRTCs in urine highlights its potential for monitoring DRTC dynamics following transplantation.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"10 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147454591","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}
Pub Date : 2026-03-09DOI: 10.1016/j.ajt.2026.02.038
Renjie Tang, Yuan Chang, Yuqi An, Dan Shan, Shen Song, Kai Xing, Peiyuan Li, Hang Zhang, Xiumeng Hua, Xiao Chen, Ningning Zhang, Shengshou Hu, Jiangping Song
Polyamines, particularly spermidine, are well-documented for their cardiovascular protective, antitumor, and longevity-promoting properties. However, their role in heart transplantation, and specifically the contribution of T-cell polyamine metabolism to transplant acceptance, remains undefined. In this study, we integrated preclinical and clinical studies to address this gap. We found that polyamine metabolism was significantly upregulated in T cells during acute rejection (AR) in both murine allografts and human AR samples. Critically, conditional inhibition of polyamine metabolism in T cells completely prevents AR and promotes long-term graft survival. Mechanistically, we found that polyamine metabolism is crucial for the differentiation of cytotoxic CD8+ T cells. Further, this regulatory effect was mediated by polyamine-dependent hypusination of eukaryotic initiation factor 5A (eIF5A), with inhibition of T cell eIF5A hypusination recapitulating the anti-AR effects of polyamine blockade. Our study identifies T cell polyamine metabolism as a critical regulator of cytotoxic CD8+ T cell differentiation and AR in heart transplantation. Targeting this pathway holds promise as a novel therapeutic strategy for treating AR.
{"title":"Inhibition of T cell polyamine metabolism promotes transplant acceptance by modulating cytotoxic CD8+ T cell differentiation","authors":"Renjie Tang, Yuan Chang, Yuqi An, Dan Shan, Shen Song, Kai Xing, Peiyuan Li, Hang Zhang, Xiumeng Hua, Xiao Chen, Ningning Zhang, Shengshou Hu, Jiangping Song","doi":"10.1016/j.ajt.2026.02.038","DOIUrl":"https://doi.org/10.1016/j.ajt.2026.02.038","url":null,"abstract":"Polyamines, particularly spermidine, are well-documented for their cardiovascular protective, antitumor, and longevity-promoting properties. However, their role in heart transplantation, and specifically the contribution of T-cell polyamine metabolism to transplant acceptance, remains undefined. In this study, we integrated preclinical and clinical studies to address this gap. We found that polyamine metabolism was significantly upregulated in T cells during acute rejection (AR) in both murine allografts and human AR samples. Critically, conditional inhibition of polyamine metabolism in T cells completely prevents AR and promotes long-term graft survival. Mechanistically, we found that polyamine metabolism is crucial for the differentiation of cytotoxic CD8<ce:sup loc=\"post\">+</ce:sup> T cells. Further, this regulatory effect was mediated by polyamine-dependent hypusination of eukaryotic initiation factor 5A (eIF5A), with inhibition of T cell eIF5A hypusination recapitulating the anti-AR effects of polyamine blockade. Our study identifies T cell polyamine metabolism as a critical regulator of cytotoxic CD8<ce:sup loc=\"post\">+</ce:sup> T cell differentiation and AR in heart transplantation. Targeting this pathway holds promise as a novel therapeutic strategy for treating AR.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"78 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147392826","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}
Pub Date : 2026-03-07DOI: 10.1016/j.ajt.2026.03.006
Allan D Kirk,Sandy Feng,Philip F Halloran
{"title":"AJT at 25 years: A trusted voice.","authors":"Allan D Kirk,Sandy Feng,Philip F Halloran","doi":"10.1016/j.ajt.2026.03.006","DOIUrl":"https://doi.org/10.1016/j.ajt.2026.03.006","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"49 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381282","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}
Pub Date : 2026-03-07DOI: 10.1016/j.ajt.2026.02.015
David K.C. Cooper
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