{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T16:15:00Z","timestamp":1783008900925,"version":"3.54.5"},"reference-count":77,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T00:00:00Z","timestamp":1586995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["1R01HL147884"],"award-info":[{"award-number":["1R01HL147884"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000983","name":"Mary Kay Foundation","doi-asserted-by":"publisher","award":["017-29"],"award-info":[{"award-number":["017-29"]}],"id":[{"id":"10.13039\/100000983","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009634","name":"Susan G. 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Keelan, Jr., MD, Research Foundation Grant","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Cardiovascular Center at the Medical College of Wisconsin","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>While radiation therapy (RT) can improve cancer outcomes, it can lead to radiation-induced heart dysfunction (RIHD) in patients with thoracic tumors. This study examines the role of adaptive immune cells in RIHD. In Salt-Sensitive (SS) rats, image-guided whole-heart RT increased cardiac T-cell infiltration. We analyzed the functional requirement for these cells in RIHD using a genetic model of T- and B-cell deficiency (interleukin-2 receptor gamma chain knockout (IL2RG\u2212\/\u2212)) and observed a complex role for these cells. Surprisingly, while IL2RG deficiency conferred protection from cardiac hypertrophy, it worsened heart function via echocardiogram three months after a large single RT dose, including increased end-systolic volume (ESV) and reduced ejection fraction (EF) and fractional shortening (FS) (p &lt; 0.05). Fractionated RT, however, did not yield similarly increased injury. Our results indicate that T cells are not uniformly required for RIHD in this model, nor do they account for our previously reported differences in cardiac RT sensitivity between SS and SS.BN3 rats. The increasing use of immunotherapies in conjunction with traditional cancer treatments demands better models to study the interactions between immunity and RT for effective therapy. We present a model that reveals complex roles for adaptive immune cells in cardiac injury that vary depending on clinically relevant factors, including RT dose\/fractionation, sex, and genetic background.<\/jats:p>","DOI":"10.3390\/cancers12040983","type":"journal-article","created":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T13:01:39Z","timestamp":1587042099000},"page":"983","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Acquired Immunity Is Not Essential for Radiation-Induced Heart Dysfunction but Exerts a Complex Impact on Injury"],"prefix":"10.3390","volume":"12","author":[{"given":"Rachel A.","family":"Schlaak","sequence":"first","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Frei","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Fish","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leanne","family":"Harmann","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiovascular Medicine, Medical College of Wisconsin, Milwaukee WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy","family":"Gasperetti","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie L.","family":"Pipke","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunguang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hallgeir","family":"Rui","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Flister","sequence":"additional","affiliation":[{"name":"Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Genomic Sciences and Precision Medicine Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin N.","family":"Gantner","sequence":"additional","affiliation":[{"name":"Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Department of Medicine, Division of Endocrinology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0886-5055","authenticated-orcid":false,"given":"Carmen","family":"Bergom","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.ijrobp.2009.09.064","article-title":"Radiation-Related Heart Disease: Current Knowledge and Future Prospects","volume":"76","author":"Darby","year":"2010","journal-title":"Int. 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