{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T05:32:43Z","timestamp":1793424763261,"version":"4.5.0"},"reference-count":24,"publisher":"Radiation Research Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2023,11,21]]},"abstract":"<jats:p>The numbers of naive T cells that react to novel pathogens not yet encountered by an immune system, decrease during aging, mainly due to age-associated involution of the thymus. CD45RA+ naive CD4 T cells consist of heterogeneous populations, including highly CXCR3-expressing cells that appear during the homeostatic proliferation of naive T cells and exhibit enhanced type-1 inflammatory phenotypes. Based on previous evidence of radiation-associated reductions in thymic function and peripheral blood naive CD4 T cells, we hypothesized that the homeostatic proliferation of naive CD4 T cells compensates for deficits in peripheral T-cell populations after radiation injury, which may increase the proportion of CXCR3high cells in naive CD4 T cells and enhance inflammation. The statistical models employed in this study revealed positive associations between the number of CXCR3high naive CD4 T cells and age as well as radiation dose among 580 Hiroshima atomic bomb survivors. In addition, the CXCR3high cells in these survivors increased not only with the levels of homeostatic cytokines, IL6 and IL7, but also with those of inflammatory indicators, CXCL10 and CRP. These results suggest that thymic T-cell production deficiency due to radiation and aging results in enhanced homeostatic proliferation that drives the appearance of CXCR3high naive CD4 T cells poised for an inflammatory response. Molecular mechanisms and clinical relevance of increasing CXCR3high cells in naive CD4 T populations should be further investigated in the context of inflammatory disease development long after radiation exposure.<\/jats:p>","DOI":"10.1667\/rade-23-00065.1","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T18:19:04Z","timestamp":1700590744000},"page":"71-76","source":"Crossref","is-referenced-by-count":2,"title":["Naive CD4 T Cells Highly Expressing the Inflammatory Chemokine Receptor CXCR3 Increase with Age and Radiation Exposure in Atomic Bomb Survivors"],"prefix":"10.1667","volume":"201","author":[{"given":"Kengo","family":"Yoshida","sequence":"first","affiliation":[{"name":"Departments of Molecular Biosciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munechika","family":"Misumi","sequence":"additional","affiliation":[{"name":"Departments of Statistics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Yamaoka","sequence":"additional","affiliation":[{"name":"Departments of Molecular Biosciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seishi","family":"Kyoizumi","sequence":"additional","affiliation":[{"name":"Departments of Molecular Biosciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waka","family":"Ohishi","sequence":"additional","affiliation":[{"name":"Departments of Clinical Studies"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Sugiyama","sequence":"additional","affiliation":[{"name":"Departments of Epidemiology, Radiation Effects Research Foundation, Hiroshima"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonori","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Departments of Molecular Biosciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichiro","family":"Kusunoki","sequence":"additional","affiliation":[{"name":"Departments of Molecular Biosciences"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"20","doi-asserted-by":"crossref","unstructured":"G Desdin-Mico, G Soto-Heredero, JF Aranda, et al.  \"Science.\"  368, \"T cells with dysfunctional mitochondria induce multimorbidity and premature senescence.\" 1371 (2020)","DOI":"10.1126\/science.aax0860"},{"key":"14","doi-asserted-by":"crossref","unstructured":"HM Cullings, EJ Grant, SD Egbert, et al.  \"Health Phys.\"  112, \"DS02R1: Improvements to atomic bomb survivors' input data and implementation of Dosimetry System 2002 (DS02) and resulting changes in estimated doses.\" 56 (2017)","DOI":"10.1097\/HP.0000000000000598"},{"key":"23","doi-asserted-by":"crossref","unstructured":"Y Kusunoki, M Yamaoka, F Kasagi, et al.  \"Radiat Res.\"  158, \"T cells of atomic bomb survivors respond poorly to stimulation by Staphylococcus aureus toxins in vitro: does this stem from their peripheral lymphocyte populations having a diminished naive CD4 T-cell content?\" 715 (2002)","DOI":"10.1667\/0033-7587(2002)158[0715:TCOABS]2.0.CO;2"},{"key":"2","doi-asserted-by":"crossref","unstructured":"Y Kusunoki, M Yamaoka, Y Kubo, et al.  \"Radiat Res.\"  174, \"T-cell immunosenescence and inflammatory response in atomic bomb survivors.\" 870 (2010)","DOI":"10.1667\/RR1847.1"},{"key":"1","doi-asserted-by":"crossref","unstructured":"M Mittelbrunn  and G Kroemer  \"Nat Immunol.\"  22, \"Hallmarks of T cell aging.\" 687 (2021)","DOI":"10.1038\/s41590-021-00927-z"},{"key":"3","doi-asserted-by":"crossref","unstructured":"K Yoshida, W Ohishi, E Nakashima, et al.  \"Hum Immunol.\"  72, \"Lymphocyte subset characterization associated with persistent hepatitis C virus infection and subsequent progression of liver fibrosis.\" 821 (2011)","DOI":"10.1016\/j.humimm.2011.05.029"},{"key":"5","doi-asserted-by":"crossref","unstructured":"K Yoshida, M Misumi, Y Kubo, et al.  \"Radiat Res.\"  186, \"Long-Term Effects of Radiation Exposure and Metabolic Status on Telomere Length of Peripheral Blood T Cells in Atomic Bomb Survivors.\" 367 (2016)","DOI":"10.1667\/RR14389.1"},{"key":"7","doi-asserted-by":"crossref","unstructured":"MP Davenport, NL Smith, BD. Rudd,  \"Nat Rev Immunol.\"  20, \"Building a T cell compartment: how immune cell development shapes function.\" 499 (2020)","DOI":"10.1038\/s41577-020-0332-3"},{"key":"8","doi-asserted-by":"crossref","unstructured":"K Song, RL Rabin, BJ Hill, et al.  \"Proc Natl Acad Sci U S A.\"  102, \"Characterization of subsets of CD4+ memory T cells reveals early branched pathways of T cell differentiation in humans.\" 7916 (2005)","DOI":"10.1073\/pnas.0409720102"},{"key":"9","doi-asserted-by":"crossref","unstructured":"V Orlando, MP La Manna, D Goletti, et al.  \"Front Immunol.\"  9, \"Human CD4 T-Cells With a Naive Phenotype Produce Multiple Cytokines During Mycobacterium Tuberculosis Infection and Correlate With Active Disease.\" 1119 (2018)","DOI":"10.3389\/fimmu.2018.01119"},{"key":"10","doi-asserted-by":"crossref","unstructured":"G De Simone, EMC Mazza, A Cassotta, et al.  \"J Immunol.\"  203, \"CXCR3 Identifies Human Naive CD8(+) T Cells with Enhanced Effector Differentiation Potential.\" 3179 (2019)","DOI":"10.4049\/jimmunol.1901072"},{"key":"11","doi-asserted-by":"crossref","unstructured":"I Gomez, U Hainz, B Jenewein, et al.  \"Mech Ageing Dev.\"  124, \"Changes in the expression of CD31 and CXCR3 in CD4+ naive T cells in elderly persons.\" 395 (2003)","DOI":"10.1016\/S0047-6374(03)00014-9"},{"key":"12","doi-asserted-by":"crossref","unstructured":"A Kato, A Takaori-Kondo, N Minato, et al.  \"Eur J Immunol.\"  48, \"CXCR3(high) CD8(+) T cells with naive phenotype and high capacity for IFN-gamma production are generated during homeostatic T-cell proliferation.\" 1663 (2018)","DOI":"10.1002\/eji.201747431"},{"key":"13","doi-asserted-by":"crossref","unstructured":"K Kodama, K Mabuchi, I Shigematsu,  \"J Epidemiol.\"  6, \"A long-term cohort study of the atomic-bomb survivors.\" S95 (1996)","DOI":"10.2188\/jea.6.3sup_95"},{"key":"15","doi-asserted-by":"crossref","unstructured":"M Yamaoka, Y Kusunoki, F Kasagi, et al.  \"Radiat Res.\"  161, \"Decreases in percentages of naive CD4 and CD8 T cells and increases in percentages of memory CD8 T-cell subsets in the peripheral blood lymphocyte populations of A-bomb survivors.\" 290 (2004)","DOI":"10.1667\/RR3143"},{"key":"16","doi-asserted-by":"crossref","unstructured":"S Sawa, D Kamimura, GH Jin, et al.  \"J Exp Med.\"  203, \"Autoimmune arthritis associated with mutated interleukin (IL)-6 receptor gp130 is driven by STAT3\/IL-7-dependent homeostatic proliferation of CD4+ T cells.\" 1459 (2006)","DOI":"10.1084\/jem.20052187"},{"key":"18","doi-asserted-by":"crossref","unstructured":"H Zhang, CM Weyand, JJ Goronzy,  \"FEBS J.\"  288, \"Hallmarks of the aging T-cell system.\" 7123 (2021)","DOI":"10.1111\/febs.15770"},{"key":"19","doi-asserted-by":"crossref","unstructured":"M Schank, J Zhao, L Wang, et al.  \"Cell Death Dis.\"  11, \"Telomeric injury by KML001 in human T cells induces mitochondrial dysfunction through the p53-PGC-1alpha pathway.\" 1030 (2020)","DOI":"10.1038\/s41419-020-03238-7"},{"key":"22","doi-asserted-by":"crossref","unstructured":"M Yamada, FL Wong, S Fujiwara, et al.  \"Radiat Res.\"  161, \"Non-cancer disease incidence in atomic bomb survivors, 1958-1998.\" 622 (2004)","DOI":"10.1667\/RR3183"},{"key":"24","doi-asserted-by":"crossref","unstructured":"R Saigusa, H Winkels, K. Ley,  \"Nat Rev Cardiol.\"  17, \"T cell subsets and functions in atherosclerosis.\" 387 (2020)","DOI":"10.1038\/s41569-020-0352-5"},{"key":"17","doi-asserted-by":"crossref","unstructured":"T Hayashi, Y Kusunoki, M Hakoda, et al.  \"Int J Radiat Biol.\"  79, \"Radiation dose-dependent increases in inflammatory response markers in A-bomb survivors.\" 129 (2003)","DOI":"10.1080\/0955300021000038662"},{"key":"6","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":"4","doi-asserted-by":"crossref","unstructured":"T Hayashi, Y Morishita, R Khattree, et al.  \"FASEB J.\"  26, \"Evaluation of systemic markers of inflammation in atomic-bomb survivors with special reference to radiation and age effects.\" 4765 (2012)","DOI":"10.1096\/fj.12-215228"},{"key":"21","doi-asserted-by":"crossref","unstructured":"T Hayashi, K Furukawa, Y Morishita, et al.  \"Free Radic Biol Med.\"  171, \"Intracellular reactive oxygen species level in blood cells of atomic bomb survivors is increased due to aging and radiation exposure.\" 126 (2021)","DOI":"10.1016\/j.freeradbiomed.2021.05.017"}],"container-title":["Radiation Research"],"original-title":[],"link":[{"URL":"https:\/\/meridian.allenpress.com\/radiation-research\/article-pdf\/doi\/10.1667\/RADE-23-00065.1\/3291850\/10.1667_rade-23-00065.1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/meridian.allenpress.com\/radiation-research\/article-pdf\/doi\/10.1667\/RADE-23-00065.1\/3291850\/10.1667_rade-23-00065.1.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T05:06:13Z","timestamp":1793423173000},"score":1,"resource":{"primary":{"URL":"https:\/\/bioone.org\/journals\/radiation-research\/volume-201\/issue-1\/RADE-23-00065.1\/Naive-CD4-T-Cells-Highly-Expressing-the-Inflammatory-Chemokine-Receptor\/10.1667\/RADE-23-00065.1.full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,21]]},"references-count":24,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1,1]]}},"URL":"https:\/\/doi.org\/10.1667\/rade-23-00065.1","relation":{},"ISSN":["0033-7587","1938-5404"],"issn-type":[{"value":"0033-7587","type":"print"},{"value":"1938-5404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,21]]}}}