{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T08:48:13Z","timestamp":1793090893754,"version":"4.5.0"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"13","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Australian National Health and Medical Research Council"},{"DOI":"10.13039\/100009930","name":"NHF","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009930","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>T cells drive adverse cardiac inflammation and ischemia-reperfusion injury following myocardial infarction (MI). Here, we aimed to test the extent to which T cell inhibition protected cardiac function following MI in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Cardiac ischemia-reperfusion injury (CIRI), mimicking MI with successful reperfusion therapy, was induced in C57BL\/6J mice via temporary surgical ligation of the left anterior descending artery. T cell inhibition was achieved using abatacept, an FDA-approved CTLA-4-Ig fusion protein. Multiple treatment strategies were assessed, ranging from prolonged treatment across 4 weeks to short-term treatment, also with delayed time-to-intervention. Cardiac function was assessed using echocardiography, including strain analysis. Impacts on the cardiac and systemic immune response were assessed using flow cytometry. CIRI-induced robust CD4+ biased T cell activation in the heart within 7 days. Treatment with abatacept significantly preserved key echocardiographic metrics of cardiac function. This treatment coincided with near-complete inhibition of the cardiac T cell response, as well as reductions in innate inflammatory cells. Collectively, this demonstrated a central mechanistic role for T cell activation post-MI with reperfusion. Evaluation of short-term intervention strategies further demonstrated sustained preservation of cardiac function even where treatment was delayed by 24\u2005h. Mechanistically, our data indicate that over 50% of lost cardiac function post-MI with reperfusion is T cell dependent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>T cell co-stimulation leading to activation is a central driver of the cardiac immune response following MI with reperfusion. The inhibition of this axis significantly protected against CIRI and preserved cardiac function. Ultimately, we highlight T cell immunomodulation and abatacept as highly promising approaches for clinical translation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvaf165","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T12:08:24Z","timestamp":1758888504000},"page":"2082-2094","source":"Crossref","is-referenced-by-count":5,"title":["CTLA-4-Ig therapy preserves cardiac function following myocardial infarction with reperfusion"],"prefix":"10.1093","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9173-0903","authenticated-orcid":false,"given":"Jonathan","family":"Noonan","sequence":"first","affiliation":[{"name":"Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute , 75 Commercial Road, Melbourne, VIC 3004 ,","place":["Australia"]},{"name":"Baker Department of Cardiometabolic Health, University of Melbourne , Parkville, VIC 3010 ,","place":["Australia"]},{"name":"Department of Immunology, School of Translational Medicine, Monash University , 99 Commercial Road, Melbourne, VIC 3004 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shania A","family":"Prijaya","sequence":"additional","affiliation":[{"name":"Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute , 75 Commercial Road, Melbourne, VIC 3004 ,","place":["Australia"]},{"name":"Baker Department of Cardiometabolic Health, University of Melbourne , Parkville, VIC 3010 ,","place":["Australia"]},{"name":"Molecular Imaging and Nanotherapeutics Laboratory, Baker Heart and Diabetes Institute , 75 Commercial Road, Melbourne, VIC 3004 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A","family":"Bienvenu","sequence":"additional","affiliation":[{"name":"Molecular Imaging and Nanotherapeutics Laboratory, Baker Heart and Diabetes Institute , 75 Commercial Road, Melbourne, VIC 3004 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1863-092X","authenticated-orcid":false,"given":"Nalin H","family":"Dayawansa","sequence":"additional","affiliation":[{"name":"Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute , 75 Commercial Road, Melbourne, VIC 3004 ,","place":["Australia"]},{"name":"Department of Medicine, School of Translational Medicine, Monash University , 99 Commercial Road, Melbourne, VIC 3004 ,","place":["Australia"]},{"name":"Department of Cardiology, The Alfred Hospital , 55 Commercial Road, Melbourne, VIC 3004 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Michla","sequence":"additional","affiliation":[{"name":"Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute , 75 Commercial Road, Melbourne, VIC 3004 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,","place":["Australia"]},{"name":"Molecular Imaging and Nanotherapeutics Laboratory, Baker Heart and Diabetes Institute , 75 Commercial Road, Melbourne, VIC 3004 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Huang","sequence":"additional","affiliation":[{"name":"Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute , 75 Commercial Road, Melbourne, VIC 3004 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Barbaro-Wahl","sequence":"additional","affiliation":[{"name":"Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute , 75 Commercial Road, Melbourne, VIC 3004 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilu","family":"Huang","sequence":"additional","affiliation":[{"name":"Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute , 75 Commercial Road, Melbourne, VIC 3004 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute , 75 Commercial Road, Melbourne, VIC 3004 ,","place":["Australia"]},{"name":"Molecular Imaging and Nanotherapeutics Laboratory, Baker Heart and Diabetes Institute , 75 Commercial Road, Melbourne, VIC 3004 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Molecular Imaging and Nanotherapeutics Laboratory, Baker Heart and Diabetes Institute , 75 Commercial Road, Melbourne, VIC 3004 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7039-7777","authenticated-orcid":false,"given":"Andrew J","family":"Murphy","sequence":"additional","affiliation":[{"name":"Baker Department of Cardiometabolic Health, University of Melbourne , Parkville, VIC 3010 ,","place":["Australia"]},{"name":"Haematopoiesis and Leukocyte Biology Laboratory, Baker Heart and Diabetes Institute , 75 Commercial Road, Melbourne, VIC 3004 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Baker Department of Cardiometabolic Health, University of Melbourne , Parkville, VIC 3010 ,","place":["Australia"]},{"name":"Haematopoiesis and Leukocyte Biology Laboratory, Baker Heart and Diabetes Institute , 75 Commercial Road, Melbourne, VIC 3004 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man K S","family":"Lee","sequence":"additional","affiliation":[{"name":"Haematopoiesis and Leukocyte Biology Laboratory, Baker Heart and Diabetes Institute , 75 Commercial Road, Melbourne, VIC 3004 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad J","family":"Johnson","sequence":"additional","affiliation":[{"name":"Bioimaging Platform, La Trobe University , Bundoora, VIC 3083 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M D","family":"Watson","sequence":"additional","affiliation":[{"name":"Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute , 75 Commercial Road, Melbourne, VIC 3004 ,","place":["Australia"]},{"name":"Department of Diabetes, School of Translational Medicine, Monash University , 99 Commercial Road, Melbourne, VIC 3004 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita C","family":"Thomas","sequence":"additional","affiliation":[{"name":"Translational Cardiology Centre, Baker Heart and Diabetes Institute , 75 Commercial Road, Melbourne, VIC 3004 ,","place":["Australia"]},{"name":"Heart Centre, The Alfred Hospital , 55 Commercial Road, Melbourne, VIC 3004 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D","family":"McFadyen","sequence":"additional","affiliation":[{"name":"Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute , 75 Commercial Road, Melbourne, VIC 3004 ,","place":["Australia"]},{"name":"Baker Department of Cardiometabolic Health, University of Melbourne , Parkville, VIC 3010 ,","place":["Australia"]},{"name":"Department of Clinical Haematology, School of Translational Medicine, Monash University , 99 Commercial Road, Melbourne, VIC 3004 ,","place":["Australia"]},{"name":"Australian Centre for Blood Diseases, School of Translational Medicine, Monash University , 99 Commercial Road, Melbourne, VIC 3004 ,","place":["Australia"]},{"name":"Baker Department of Cardiovascular Research, Translational and Implementation, La Trobe University , 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