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While prior studies have explored radiation-induced disruptions in immune homeostasis, the direct effect of WBI on pre-existing memory CD4 T cells remains elusive. Using T cell receptor transgenic CD4 T cell chimeric mice infected with lymphocytic choriomeningitis virus\u2013Armstrong, we demonstrate that a sublethal WBI dose (5\u2009Gy) causes a significant and persistent reduction in the numbers of memory CD4 T cells for at least 30\u2009d post-WBI. At 8\u2009d post-WBI, memory CD4 T cells exhibited an increased frequency of Ly6C+ T helper 1 cells and a decreased frequency of PSGL1+Ly6C\u2212 central memory cells in the spleen compared with mock-irradiated (0\u2009Gy) control mice. These subset imbalances were no longer detectable by 30\u2009d post-WBI. However, surviving memory CD4 T cells exhibited intrinsic functional impairments, including reduced production of the proinflammatory cytokines IFN\u03b3, TNF\u03b1, and IL-2 upon ex vivo stimulation with the gp61\u201380 peptide. Furthermore, irradiated T cell receptor transgenic memory CD4 T cells exhibited defective secondary expansion upon pathogen re-encounter in unmanipulated hosts. Finally, the irradiated primary memory CD4 T cells exhibited poor protection potential, as they were unable to clear the pathogen upon re-exposure as effectively as their 0\u2009Gy counterpart. In summary, sublethal WBI impairs the kinetics, subset composition, and function of memory CD4 T cells, ultimately compromising their ability to mount effective recall responses to clear the infection.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag244","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T22:24:43Z","timestamp":1789079083000},"source":"Crossref","is-referenced-by-count":0,"title":["Virus-specific memory CD4 T cells sustain long-term numerical and functional impairment following whole-body irradiation"],"prefix":"10.1093","volume":"215","author":[{"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 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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":"John T","family":"Harty","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":"Experimental Pathology Graduate Program, Carver College of Medicine, University of Iowa , Iowa City, IA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir P","family":"Badovinac","sequence":"additional","affiliation":[{"name":"Interdisciplinary Graduate Program in Immunology, Carver College of Medicine, University of Iowa , Iowa City, IA,","place":["United 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