{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T04:51:28Z","timestamp":1782449488880,"version":"3.54.5"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Thymopoiesis plays a critical role in shaping the peripheral T-cell repertoire during childhood. Following pediatric liver transplantation, patients receive intensive immunosuppressive therapy, which may disrupt thymic function; however, thymic involvement after solid organ transplantation remains poorly understood. This prospective study aimed to assess the impact of immunosuppressive therapy on thymic function and morphology in pediatric first-time liver transplant recipients over a one-year follow-up period. The primary endpoint was thymic output, quantified by sjTRECs. Secondary endpoints included intrathymic proliferation (sj\/\u03b2TREC ratio), recent thymic emigrants (RTEs; CD3\n                    <jats:sup>+<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD45RA\n                    <jats:sup>+<\/jats:sup>\n                    CD31\n                    <jats:sup>+<\/jats:sup>\n                    ), and thymic morphology. All parameters were assessed at baseline (pre-transplant) and at 1, 3, 6, and 12 months post-transplantation. Twelve patients were included. The primary endpoint -thymic output measured by sjTRECs- declined significantly over the 12-month follow-up (\u03b2=-732.1, p&amp;lt;0.01). Among secondary endpoints, the sj\/\u03b2TREC ratio, showed a significant reduction after 3 months post-transplant. The frequency of recent thymic emigrants (RTEs) showed a decreasing trend that did not reach statistical significance, although RTEs correlated positively with sjTREC levels. Thymic size assessed by ultrasound decreased significantly at 3 months, with partial recovery thereafter. Taken together, our findings provide preliminary evidence of early and persistent changes in markers of thymic function following immunosuppression after pediatric liver transplantation. Although the small sample size and exploratory design of this pilot study warrant cautious interpretation, the statistically significant changes observed in the primary endpoint justify the need for further controlled studies to better characterize the impact of immunosuppressive therapy on thymic recovery and long-term immune reconstitution in pediatric transplant recipients.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1864634","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T04:40:24Z","timestamp":1782448824000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunosuppression after pediatric liver transplantation may lead to early and prolonged acute thymic involution: findings from a pilot longitudinal study"],"prefix":"10.3389","volume":"17","author":[{"given":"Guillermo","family":"Costaguta","sequence":"first","affiliation":[{"name":"Pediatric Gastroenterology, Hepatology, and Nutrition, CHU de Quebec-Universit\u00e9 Laval","place":["Quebec, QC, Canada"]},{"name":"Research Centre of CHU de Quebec-Universit\u00e9 Laval","place":["Quebec, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Dinatale","sequence":"additional","affiliation":[{"name":"Instituto de Inmunolog\u00eda Cl\u00ednica y Experimental de Rosario (IDICER-CONICET-UNR)","place":["Rosario, Argentina"]},{"name":"Facultad de Ciencias M\u00e9dicas, Universidad Nacional de Rosario","place":["Rosario, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itau\u00e1 Leston","family":"Araujo","sequence":"additional","affiliation":[{"name":"Laboratory on Thymus Research and National Institute of Science and Technology on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilson","family":"Savino","sequence":"additional","affiliation":[{"name":"Laboratory on Thymus Research and National Institute of Science and Technology on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology, Hepatology and Nutrition of CHU Sainte-Justine","place":["Montreal, QC, Canada"]},{"name":"Department of Pediatrics, University of Montreal","place":["Montreal, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Bottasso","sequence":"additional","affiliation":[{"name":"Instituto de Inmunolog\u00eda Cl\u00ednica y Experimental de Rosario (IDICER-CONICET-UNR)","place":["Rosario, Argentina"]},{"name":"Facultad de Ciencias M\u00e9dicas, Universidad Nacional de Rosario","place":["Rosario, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Rosa","family":"Perez","sequence":"additional","affiliation":[{"name":"Instituto de Inmunolog\u00eda Cl\u00ednica y Experimental de Rosario (IDICER-CONICET-UNR)","place":["Rosario, Argentina"]},{"name":"Facultad de Ciencias M\u00e9dicas, Universidad Nacional de Rosario","place":["Rosario, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florencia Bel\u00e9n","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Instituto de Inmunolog\u00eda Cl\u00ednica y Experimental de Rosario (IDICER-CONICET-UNR)","place":["Rosario, Argentina"]},{"name":"Facultad de Ciencias M\u00e9dicas, Universidad Nacional de Rosario","place":["Rosario, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Costaguta","sequence":"additional","affiliation":[{"name":"Liver Transplantation Unit, Sanatorio de Ni\u00f1os de Rosario","place":["Rosario, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-96400-3_31","article-title":"Immunosuppression in pediatric liver transplant","volume-title":"Pediatric Hepatology and Liver Transplantation","author":"Mckiernan","year":"2019"},{"key":"B2","unstructured":"Res\u00famen estad\u00edstico"},{"key":"B3","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1002\/LT.23697","article-title":"Long-term medical management of the pediatric patient after liver transplantation: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation","volume":"19","author":"Kelly","year":"2013","journal-title":"Liver Transpl"},{"key":"B4","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.bpg.2017.03.001","article-title":"Modification of immunosuppressive therapy as risk factor for complications after liver transplantation","volume":"31","author":"De Simone","year":"2017","journal-title":"Best Pract Res Clin Gastroenterol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/HEP.26426","article-title":"Prospective multicenter clinical trial of immunosuppressive drug withdrawal in stable adult liver transplant recipients","volume":"58","author":"Ben\u00edtez","year":"2013","journal-title":"Hepatology"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1001\/JAMA.2011.2014","article-title":"Complete immunosuppression withdrawal and subsequent allograft function among pediatric recipients of parental living donor liver transplants","volume":"307","author":"Feng","year":"2012","journal-title":"JAMA"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114507832880","article-title":"The thymus is a common target in malnutrition and infection","volume":"98","author":"Savino","year":"2007","journal-title":"Br J Nutr"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1159\/000081429","article-title":"Epithelial framework reorganization during human thymus involution","volume":"51","author":"Marinova","year":"2005","journal-title":"Gerontology"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2009.05.001","article-title":"An evolutionary perspective on the mechanisms of immunosenescence","volume":"30","author":"Shanley","year":"2009","journal-title":"Trends Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PPAT.0020062","article-title":"The thymus is a common target organ in infectious diseases","volume":"2","author":"Savino","year":"2006","journal-title":"PloS Pathog"},{"key":"B11","doi-asserted-by":"crossref","DOI":"10.1007\/978-94-017-8712-3_6","article-title":"Thymic maturation and programmed cell death","volume-title":"Eco-Immunology: Evolutive Aspects and Future Perspectives","author":"Quaglino","year":"2014"},{"key":"B12","article-title":"Apoptosis of human T-cells: induction by glucocorticoids or surface receptor ligation in vitro and ex vivo","volume-title":"J Biol Regul Homeost Agents","author":"Ara\u00fajo","year":"1999"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2014.01.004","article-title":"Reduced thymic output in elite athletes","volume":"39","author":"Prieto-Hinojosa","year":"2014","journal-title":"Brain Behav Immun"},{"key":"B14","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1677\/JOE.1.06642","article-title":"Endogenous glucocorticoids cause thymus atrophy but are protective during acute Trypanosoma cruzi infection","volume":"190","author":"Roggero","year":"2006","journal-title":"J Endocrinol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1429912","article-title":"Systemic immunostimulation induces glucocorticoid-mediated thymic involution succeeded by rebound hyperplasia which is impaired in aged recipients","volume":"15","author":"Collins","year":"2024","journal-title":"Front Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PONE.0072801","article-title":"Interleukin-21 accelerates thymic recovery from glucocortico\u00efd-induced atrophy","volume":"8","author":"Rafei","year":"2013","journal-title":"PloS One"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1152\/AJPHEART.00195.2024","article-title":"Glucocorticoids impair T lymphopoiesis after myocardial infarction","volume":"327","author":"Shane","year":"2024","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01341","article-title":"Evaluating thymic function after human hematopoietic stem cell transplantation in the personalized medicine era","volume":"11","author":"Gaballa","year":"2020","journal-title":"Front Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1080\/146532402320776035","article-title":"The contribution of the thymus to immune reconstitution after hematopoietic stem-cell transplantation","volume":"4","author":"Douek","year":"2002","journal-title":"Cytotherapy"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/25374","article-title":"Changes in thymic function with age and during the treatment of HIV infection","volume":"396","author":"Douek","year":"1998","journal-title":"Nature"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1086\/320197","article-title":"Evaluation of T cell receptor gene rearrangement excision circles after antiretroviral therapy in children infected with human immunodeficiency virus","volume":"183","author":"Chavan","year":"2001","journal-title":"J Infect Dis"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/J.JIM.2009.11.007","article-title":"A reliable and simplified sj\/\u03b2-TREC ratio quantification method for human thymic output measurement","volume":"352","author":"Ferrando-Mart\u00ednez","year":"2010","journal-title":"J Immunol Methods"},{"key":"B23","doi-asserted-by":"publisher","first-page":"255","DOI":"10.34894\/VQ1DJA","article-title":"Genetic and environmental determination of thymic function in healthy immune response","author":"Rigneault","year":"2019","journal-title":"Focus Microscopy"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.2214\/AJR.161.1.8517295","article-title":"Sonography of the thymus in healthy children: frequency of visualization, size, and appearance","volume":"161","author":"Adam","year":"1993","journal-title":"AJR Am J Roentgenol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.4049\/JIMMUNOL.174.11.7446","article-title":"The influence of age on T cell generation and TCR diversity","volume":"174","author":"Naylor","year":"2005","journal-title":"J Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1126\/SCIADV.AEB2970","article-title":"Age-related thymic involution: Mechanistic insights and rejuvenating approaches to restore immune function","volume":"12","author":"Santamaria","year":"2026","journal-title":"Sci Adv"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/J.BBAMCR.2007.05.006","article-title":"Up-regulation of VEGF expression by NGF that enhances reparative angiogenesis during thymic regeneration in adult rat","volume":"1773","author":"Park","year":"2007","journal-title":"Biochim Biophys Acta (BBA) - Mol Cell Res"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2021.706244","article-title":"Thymus degeneration and regeneration","volume":"12","author":"Duah","year":"2021","journal-title":"Front Immunol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1002\/IID3.60","article-title":"Bacterial clearance reverses a skewed T-cell repertoire induced by Salmonella infection","volume":"3","author":"Leyva-Rangel","year":"2015","journal-title":"Immun Inflammation Dis"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2015.07.012","article-title":"HP-PRRSV is attenuated by de-optimization of codon pair bias in its RNA-dependent RNA polymerase nsp9 gene","volume":"485","author":"Gao","year":"2015","journal-title":"Virology"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2020.01838","article-title":"The thymus in Chagas disease: Molecular interactions involved in abnormal T-cell migration and differentiation","volume":"11","author":"P\u00e9rez","year":"2020","journal-title":"Front Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/S11046-007-9074-Z","article-title":"Interactions of Paracoccidioides brasiliensis with host cells: recent advances","volume":"165","author":"Mendes-Giannini","year":"2008","journal-title":"Mycopathologia"},{"key":"B33","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1002\/PHAR.2481","article-title":"Immunosuppression trends in solid organ transplantation: The future of individualization, monitoring, and management","volume":"41","author":"Pilch","year":"2020","journal-title":"Pharmacotherapy"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1111\/J.1399-0039.2011.01820.X","article-title":"Thymus and immune reconstitution after allogeneic hematopoietic stem cell transplantation in humans: never say never again","volume":"79","author":"Toubert","year":"2012","journal-title":"Tissue Antigens"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1080\/10245332.2017.1327504","article-title":"Pre-transplantation thymic function is associated with the risk of acute graft versus host disease and cytomegalovirus viremia after allogeneic hematopoietic stem cell transplantation","volume":"23","author":"Yang","year":"2018","journal-title":"Hematology"},{"key":"B36","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1046\/J.1365-2141.2003.04482.X","article-title":"T-cell receptor excision circles: a novel prognostic parameter for the outcome of transplantation in multiple myeloma patients","volume":"122","author":"Svaldi","year":"2003","journal-title":"Br J Haematol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2011.12.001","article-title":"Thymic function after allogeneic stem cell transplantation is dependent on graft source and predictive of long term survival","volume":"142","author":"Sairafi","year":"2012","journal-title":"Clin Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01653","article-title":"Pre-transplant thymic function predicts is associated with patient death after kidney transplantation","volume":"11","author":"Courivaud","year":"2020","journal-title":"Front Immunol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/S12979-020-00175-Z","article-title":"A very low thymus function identifies patients with substantial increased risk for long-term mortality after kidney transplantation","volume":"17","author":"Betjes","year":"2020","journal-title":"Immun Ageing"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1714478115","article-title":"Thymic involution and rising disease incidence with age","volume":"115","author":"Palmer","year":"2018","journal-title":"Proc Natl Acad Sci USA"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1007\/S11357-025-01555-3","article-title":"Measuring thymic output across the human lifespan: a critical challenge in laboratory medicine","volume":"47","author":"Middelkamp","year":"2025","journal-title":"Geroscience"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/J.CLIM.2004.12.008","article-title":"Multiparameter evaluation of human thymic function: interpretations and caveats","volume":"115","author":"Harris","year":"2005","journal-title":"Clin Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00481","article-title":"Assessment of thymic output dynamics after in utero infection of mice with Coxsackievirus B4","volume":"11","author":"Halouani","year":"2020","journal-title":"Front Immunol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"2999","DOI":"10.1182\/BLOOD-2008-07-166223","article-title":"IL-7 sustains CD31 expression in human naive CD4+ T cells and preferentially expands the CD31+ subset in a PI3K-dependent manner","volume":"113","author":"Azevedo","year":"2009","journal-title":"Blood"},{"key":"B45","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1038\/s41586-026-10242-y","article-title":"Thymic health consequences in adults","volume":"652","author":"Bernatz","year":"2026","journal-title":"Nature"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanwpc.2025.101615","article-title":"Thymic characteristics in patients with autoimmune diseases: a multicentre radiological observational study","volume":"60","author":"Chang","year":"2025","journal-title":"Lancet Reg Health West Pac"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1111\/sji.13418","article-title":"Long-term immunological changes after corrective cardiac surgery","volume":"100","author":"Bilgic-Eltan","year":"2024","journal-title":"Scand J Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1864634\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T04:40:59Z","timestamp":1782448859000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1864634\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,26]]},"references-count":47,"alternative-id":["10.3389\/fimmu.2026.1864634"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1864634","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,26]]},"article-number":"1864634"}}