{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:51:22Z","timestamp":1791244282135,"version":"4.1.0"},"reference-count":57,"publisher":"Radiation Research Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2025,8,20]]},"abstract":"<jats:p>The thymus is critical for the development and selection of T cells with a diverse range of non-self-reactive antigen receptors. Both the thymus and circulating T cells can be damaged by acute exposure to ionizing radiation, leading to dose-dependent lymphopenia, a temporarily increased risk of infection that can be life-threatening, and long-term disruptions in T cell homeostasis and function. Currently, there are no biomedical countermeasures available to prevent radiation-induced T cell lymphopenia or other T cell defects caused by radiation. Therefore, preclinical models of radiation-induced thymic injury are necessary for testing countermeasures. Adult mice and non-human primates (NHP) that are subjected to whole-body or thorax irradiation are suitable models for this purpose. However, findings from these models may not directly apply to juveniles, given the significant changes in thymus size and function during childhood. To address this, we characterized the effects of 10 Gy whole-thorax irradiation on the thymus of pediatric rhesus macaque NHPs. Computed tomography (CT) assessments of thymic density and volume were used as in vivo indicators of thymic injury, but they did not correlate with the changes in thymic weight observed 19 weeks after irradiation. Histopathological staining revealed that whole-thorax irradiation caused disruption of thymic architecture, evident four months post-irradiation in some animals. Molecular analyses showed that radiation led to a decrease in thymic output, reduced diversity of T cell antigen receptors, and an over-representation of certain receptor sequences indicative of extensive clonal expansion. Overall, this work demonstrates the usefulness of the NHP whole-thorax irradiation modelcommonly employed in lung radiobiology researchin studying radiation-induced thymic injury in children and in developing medical countermeasures.<\/jats:p>","DOI":"10.1667\/rade-24-00247.1","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T11:24:52Z","timestamp":1755689092000},"page":"398-407","source":"Crossref","is-referenced-by-count":1,"title":["Whole-Thorax Irradiation Induces Persistent T Cell Clonal Dysregulation in Pediatric Rhesus Macaques"],"prefix":"10.1667","volume":"204","author":[{"given":"Andrew N.","family":"Macintyre","sequence":"first","affiliation":[{"name":"Duke Human Vaccine Institute and Department of Medicine, Duke University School of Medicine, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Olson","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section on Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaya","family":"Balamayooran","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section on Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory O.","family":"Dugan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section on Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell P.","family":"O'Donnell","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section on Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sravani","family":"Venkatayogi","sequence":"additional","affiliation":[{"name":"Duke Human Vaccine Institute and Department of Medicine, Duke University School of Medicine, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Daniel","family":"Bourland","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Wiehe","sequence":"additional","affiliation":[{"name":"Duke Human Vaccine Institute and Department of Medicine, Duke University School of Medicine, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory D.","family":"Sempowski","sequence":"additional","affiliation":[{"name":"Duke Human Vaccine Institute and Department of Medicine, Duke University School of Medicine, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura P.","family":"Hale","sequence":"additional","affiliation":[{"name":"Department of Pathology and Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Mark","family":"Cline","sequence":"additional","affiliation":[{"name":"Department of Pathology and Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Caudell","sequence":"additional","affiliation":[{"name":"Department of Pathology and Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"25","doi-asserted-by":"crossref","unstructured":"TA Beach, AM Groves, JP Williams, et al.  \"Int J Radiat Biol.\"  96, \"Modeling radiation-induced lung injury: lessons learned from whole thorax irradiation.\" 129 (2020)","DOI":"10.1080\/09553002.2018.1532619"},{"key":"23","doi-asserted-by":"publisher","unstructured":"DL Caudell, KT Michalson, RN Andrews, et al.  \"Radiat Res.\"  192, \"Transcriptional profiling of non-human primate lymphoid organ responses to total-body irradiation.\" 40 (2019)","DOI":"10.1667\/RR15100.1"},{"key":"8","doi-asserted-by":"crossref","unstructured":"Y Zhuang, BY Yuan, GW Chen, et al.  \"Front Oncol.\"  9, \"Association Between Circulating Lymphocyte Populations and Outcome After Stereotactic Body Radiation Therapy in Patients With Hepatocellular Carcinoma.\" 896 (2019)","DOI":"10.3389\/fonc.2019.00896"},{"key":"9","doi-asserted-by":"crossref","unstructured":"F Mozaffari, C Lindemalm, A Choudhury, et al.  \"Br J Cancer.\"  97, \"NK-cell and T-cell functions in patients with breast cancer: effects of surgery and adjuvant chemo- and radiotherapy.\" 105 (2007)","DOI":"10.1038\/sj.bjc.6603840"},{"key":"12","doi-asserted-by":"crossref","unstructured":"OA. 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Adams, RE Shore, A Dozier, et al.  \"Radiat Res.\"  174, \"Thyroid cancer risk 40+ years after irradiation for an enlarged thymus: an update of the Hempelmann cohort.\" 753 (2010)","DOI":"10.1667\/RR2181.1"},{"key":"56","doi-asserted-by":"crossref","unstructured":"NG Hildreth, RE Shore, LH Hempelmann, et al.  \"Radiat Res.\"  102, \"Risk of extrathyroid tumors following radiation treatment in infancy for thymic enlargement.\" 378 (1985)","DOI":"10.2307\/3576713"},{"key":"19","doi-asserted-by":"crossref","unstructured":"BF Koontz, F Verhaegen, D De Ruysscher,  \"Br J Radiol.\"  90, \"Tumour and normal tissue radiobiology in mouse models: How close are mice to mini-humans?\" 20160441 (2017)","DOI":"10.1259\/bjr.20160441"},{"key":"47","doi-asserted-by":"crossref","unstructured":"SA Ghandhi, HC Turner, I Shuryak, et al.  \"PloS One.\"  13, \"Whole thorax irradiation of non-human primates induces persistent nuclear damage and gene expression changes in peripheral blood cells.\" e0191402 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\"Considerations of medical preparedness to assess and treat various populations during a radiation public health emergency.\" 301 (2023)","DOI":"10.1667\/RADE-22-00148.1"},{"key":"22","doi-asserted-by":"crossref","unstructured":"JD Estes, SW Wong, JM Brenchley,  \"Nat Rev Immunol.\"  18, \"Nonhuman primate models of human viral infections.\" 390 (2018)","DOI":"10.1038\/s41577-018-0005-7"},{"key":"36","doi-asserted-by":"crossref","unstructured":"R Ito, LP Hale, SM Geyer, et al.  \"Radiat Res.\"  187, \"Late effects of exposure to ionizing radiation and age on human thymus morphology and function.\" 589 (2017)","DOI":"10.1667\/RR4554.1"},{"key":"5","doi-asserted-by":"crossref","unstructured":"AN Macintyre, MJ French, BR Sanders, et al.  \"Adv Radiat Oncol.\"  6, \"Long-term recovery of the adaptive immune system in rhesus macaques after total body irradiation.\" 100677 (2021)","DOI":"10.1016\/j.adro.2021.100677"},{"key":"4","doi-asserted-by":"crossref","unstructured":"MJ French, R Wuerker, G Dugan, et al.  \"Int J Radiat Oncol Biol Phys.\"  115, \"Long-term immunological consequences of radiation exposure in a diverse cohort of Rhesus Macaques.\" 945 (2023)","DOI":"10.1016\/j.ijrobp.2022.10.024"}],"container-title":["Radiation 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