{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T01:54:13Z","timestamp":1792547653177,"version":"4.5.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T00:00:00Z","timestamp":1704844800000},"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:sec><jats:title>Background<\/jats:title><jats:p>Recovery and functional differentiation of T-cell subsets are central for the development of immune function and complications after allogeneic hematopoietic stem cell transplantation (HSCT), but little is known about the cellular respiration and factors influencing T-cell metabolic fitness during immune maturation after HSCT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We included 20 HSCT patients and analysed mitochondrial oxidative phosphorylation and mitochondrial fitness in peripheral blood mononuclear cell samples collected at days +90 and +180 after HSCT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Phenotypic analysis revealed lower overall T-cell counts, lower CD4+\/CD8+ ratio and a skewed distribution of early T-cell subsets at day +90, gradually recovering by day +180. Although ATP turnover in HSCT patients was similar to healthy controls, the spare respiratory capacity (SRC) of T cells, reflecting the available energy reserve, was significantly reduced at day +90 and +180 compared to healthy controls. This reduction in SRC was not correlated with the occurrence of acute graft-versus-host disease (aGVHD), the intensity of conditioning regimens and markers of T-cell exhaustion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We found significantly depressed SRC until six months post-HSCT, but we were not able to identify transplant-related risk factors or associations with the clinical outcome.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1327977","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T04:16:01Z","timestamp":1704860161000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Reduced mitochondrial respiration in peripheral T cells after paediatric heamatopoietic stem cell transplantation"],"prefix":"10.3389","volume":"14","author":[{"given":"Kasper","family":"M\u00f8lgaard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrine","family":"Kielsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Ifversen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zcan","family":"Met","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge Marie","family":"Svane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,1,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60237-3","article-title":"Graft-versus-host disease","volume":"373","author":"Ferrara","year":"2009","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8652(199702)54:2<131::AID-AJH6>3.0.CO;2-Y","article-title":"Infectious morbidity in long-term survivors of allogeneic marrow transplantation is associated with low CD4 T cell counts","volume":"54","author":"Storek","year":"1997","journal-title":"Am J Hematol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v92.11.4464","article-title":"Reconstitution of the T-cell compartment after bone marrow transplantation: Restoration of the repertoire by thymic emigrants","volume":"92","author":"Dumont-Girard","year":"1998","journal-title":"Blood"},{"key":"B4","doi-asserted-by":"publisher","first-page":"317ra198","DOI":"10.1126\/scitranslmed.aac8265","article-title":"Tracking genetically engineered lymphocytes long-term reveals the dynamics of t cell immunological memory","volume":"7","author":"Oliveira","year":"2015","journal-title":"Sci Transl Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2446","article-title":"A human memory T cell subset with stem cell-like properties","volume":"17","author":"Gattinoni","year":"2011","journal-title":"Nat Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-05-431718","article-title":"IL-7 and IL-15 instruct the generation of human memory stem T cells from naive precursors","volume":"121","author":"Cieri","year":"2013","journal-title":"Blood"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2001077","article-title":"IL-7 and IL-15 Levels Reflect the Degree of T Cell Depletion during Lymphopenia and Are Associated with an Expansion of Effector Memory T Cells after Pediatric Hematopoietic Stem Cell Transplantation","volume":"206","author":"Kielsen","year":"2021","journal-title":"J Immunol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1111\/sji.12244","article-title":"T cell reconstitution in allogeneic haematopoietic stem cell transplantation: Prognostic significance of plasma interleukin-7","volume":"81","author":"Kielsen","year":"2015","journal-title":"Scand J Immunol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.immuni.2011.12.007","article-title":"Mitochondrial respiratory capacity is a critical regulator of CD8 + T cell memory development","volume":"36","author":"van der Windt","year":"2012","journal-title":"Immunity"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.645242","article-title":"Fundamentals of T cell metabolism and strategies to enhance cancer immunotherapy","volume":"12","author":"Rangel Rivera","year":"2021","journal-title":"Front Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3791\/62984","article-title":"Real-time monitoring of mitochondrial respiration in cytokine-differentiated human primary T cells","author":"M\u00f8lgaard","year":"2021","journal-title":"J Vis Exp"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.718863","article-title":"Mitochondrial-linked de novo pyrimidine biosynthesis dictates human T-cell proliferation but not expression of effector molecules","volume":"12","author":"Peeters","year":"2021","journal-title":"Front Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/nature08097","article-title":"Enhancing CD8 T-cell memory by modulating fatty acid metabolism","volume":"460","author":"Pearce","year":"2009","journal-title":"Nature"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1172\/JCI69589","article-title":"Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function","volume":"123","author":"Sukumar","year":"2013","journal-title":"J Clin Invest"},{"key":"B15","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.coi.2017.03.011","article-title":"Metabolic reprograming of anti-tumor immunity","volume":"46","author":"Sukumar","year":"2017","journal-title":"Curr Opin Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/nm1359","article-title":"Interleukin-15 rescues tolerant CD8+ T cells for use in adoptive immunotherapy of established tumors","volume":"12","author":"Teague","year":"2006","journal-title":"Nat Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba1786","article-title":"Transient rest restores functionality in exhausted CAR-T cells through epigenetic remodeling","volume":"372","author":"Weber","year":"2021","journal-title":"Sci (80- )"},{"key":"B18","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1016\/j.cmet.2018.02.024","article-title":"Increased tumor glycolysis characterizes immune resistance to adoptive T cell therapy","volume":"27","author":"Cascone","year":"2018","journal-title":"Cell Metab"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1016\/j.cell.2013.05.016","article-title":"Posttranscriptional control of T cell effector function by aerobic glycolysis","volume":"153","author":"Chang","year":"2013","journal-title":"Cell"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1242454","DOI":"10.1126\/science.1242454","article-title":"Fueling immunity: insights into metabolism and lymphocyte function","volume":"342","author":"Pearce","year":"2013","journal-title":"Sci (80- )"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151159","article-title":"T cell metabolism drives immunity","volume":"212","author":"Buck","year":"2015","journal-title":"J Exp Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2017.10.023","article-title":"Reconstitution of Th17, Tc17 and Treg cells after paediatric haematopoietic stem cell transplantation: Impact of interleukin-7","volume":"223","author":"Kielsen","year":"2018","journal-title":"Immunobiology"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00507","article-title":"Immune reconstitution after allogeneic hematopoietic stem cell transplantation","volume":"7","author":"Ogonek","year":"2016","journal-title":"Front Immunol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1186\/s40425-019-0628-7","article-title":"PD-1 signaling affects cristae morphology and leads to mitochondrial dysfunction in human CD8+ T lymphocytes","volume":"7","author":"Ogando","year":"2019","journal-title":"J Immunother Cancer"},{"key":"B25","doi-asserted-by":"publisher","first-page":"6692","DOI":"10.1038\/ncomms7692","article-title":"PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation","volume":"6","author":"Patsoukis","year":"2015","journal-title":"Nat Commun"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-12-195792","article-title":"Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired","volume":"114","author":"Ahmadzadeh","year":"2009","journal-title":"Blood"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01034","article-title":"Dynamics of expression of programmed cell death protein-1 (PD-1) on T cells after allogeneic hematopoietic stem cell transplantation","volume":"10","author":"Simonetta","year":"2019","journal-title":"Front Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2003.10.006","article-title":"Acute and chronic graft-versus-host disease after ablative and nonmyeloablative conditioning for allogeneic hematopoietic transplantation","volume":"10","author":"Couriel","year":"2004","journal-title":"Biol Blood Marrow Transplant"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1327977\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T04:16:02Z","timestamp":1704860162000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1327977\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,10]]},"references-count":28,"alternative-id":["10.3389\/fimmu.2023.1327977"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1327977","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,10]]},"article-number":"1327977"}}