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Gray"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Whole-body irradiation (WBI) consistently induces radiation-associated lymphopenia, a complication linked to poor prognosis and reduced overall survival. Understanding the quantitative and qualitative changes in na\u00efve CD4 T cells after WBI is critical because these cells play key roles in both host defense and the propagation of autoimmunity. Here, we show that WBI triggers a rapid decline in the na\u00efve CD4 T-cell pool, followed by thymus-dependent numerical recovery. Shortly after WBI, mice exhibit a reduced frequency of lymphocytic choriomeningitis virus (LCMV) epitope GP66-77\u2013specific na\u00efve CD4 T-cell precursors. Upon infection with LCMV, this reduction leads to delayed effector expansion, impaired memory differentiation, and diminished cytokine production. WBI also disrupts blood\u2013brain barrier (BBB) integrity, enhancing infiltration of GP66-77\u2013specific memory CD4 T cells into the brain and promoting enrichment of brain-resident tissue-resident memory CD4 T cells. Similarly, encephalitogenic MOG38-49\u2013specific CD4 T-cell precursors are reduced after WBI, resulting in delayed but exacerbated experimental autoimmune encephalomyelitis (EAE) compared with nonirradiated controls. WBI-mediated BBB disruption facilitates the entry of encephalitogenic MOG38-49\u2013specific CD4 T cells into the spinal cord, promoting EAE induction and progression even in the absence of pertussis toxin administration. Together, these findings highlight both immune-intrinsic and -extrinsic effects of WBI in shaping na\u00efve CD4 T-cell responses in the context of infection and autoimmunity.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag174","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T15:15:04Z","timestamp":1783955704000},"source":"Crossref","is-referenced-by-count":1,"title":["Whole-body irradiation causes long-term impairments in the maintenance and function of na\u00efve CD4 T cells specific for self- and non-self-antigens"],"prefix":"10.1093","volume":"215","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7862-4663","authenticated-orcid":false,"given":"Shravan Kumar","family":"Kannan","sequence":"first","affiliation":[{"name":"Interdisciplinary Graduate Program in Immunology, Carver College of Medicine, University of Iowa , Iowa City, IA,","place":["United States"]},{"name":"Department of Pathology, Carver College of Medicine, University of Iowa , Iowa City, IA,","place":["United States"]},{"name":"Holden Comprehensive Cancer Center, Carver College of Medicine, University of Iowa , Iowa City, IA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ti-Ara J","family":"Turner","sequence":"additional","affiliation":[{"name":"Interdisciplinary Graduate Program in Immunology, Carver College of Medicine, University of Iowa , Iowa City, IA,","place":["United States"]},{"name":"Department of Pathology, Carver College of Medicine, University of Iowa , Iowa City, IA,","place":["United States"]},{"name":"Holden Comprehensive Cancer Center, Carver College of Medicine, University of Iowa , Iowa City, IA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Heidarian","sequence":"additional","affiliation":[{"name":"Department of Pathology, Carver College of Medicine, University of Iowa , Iowa City, IA,","place":["United States"]},{"name":"Holden 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States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caleb Y","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Immunology, University of Minnesota , Minneapolis, MN,","place":["United States"]},{"name":"Microbiology, Immunology, and Cancer Biology Program, University of Minnesota , Minneapolis, MN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8323-6419","authenticated-orcid":false,"given":"Cori","family":"Fain","sequence":"additional","affiliation":[{"name":"Department of Pathology, Carver College of Medicine, University of Iowa , Iowa City, IA,","place":["United States"]},{"name":"Holden Comprehensive Cancer Center, Carver College of Medicine, University of Iowa , Iowa City, IA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shailesh K","family":"Shahi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Carver College of Medicine, University of Iowa , Iowa City, IA,","place":["United States"]},{"name":"Holden Comprehensive Cancer Center, Carver College of Medicine, University of Iowa , Iowa City, IA,","place":["United States"]},{"name":"Experimental Pathology Graduate Program, Carver College of Medicine, University of Iowa , Iowa City, IA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A","family":"Escue","sequence":"additional","affiliation":[{"name":"Department of Pathology, Carver College of Medicine, University of Iowa , Iowa City, IA,","place":["United States"]},{"name":"Holden Comprehensive Cancer Center, Carver College of Medicine, University of Iowa , Iowa City, IA,","place":["United States"]},{"name":"Experimental Pathology Graduate Program, Carver College of Medicine, University of Iowa , Iowa City, IA,","place":["United 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