{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:57:56Z","timestamp":1792065476966,"version":"4.4.0"},"reference-count":17,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP23K14939"],"award-info":[{"award-number":["JP23K14939"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Allergy Immunology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Pediatric allergic rhinitis (AR) can substantially affect quality of life and school performance, yet conventional sensitization markers such as allergen\u2010specific immunoglobulin E (sIgE) do not consistently reflect symptom severity. We examined whether activation\u2010induced marker (AIM)\u2010defined allergen\u2010specific peripheral effector\u2010memory CD4\n +<\/jats:sup>\n T\u2010cell (peff\u2010mCD4) frequencies were associated with symptom burden.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n In this pilot, single\u2010center observational study, house dust mite (HDM)\u2010specific responses were analyzed in 20 children and Japanese cedar pollen (JCP)\u2010specific responses in 19. Nasal symptom numerical rating scale (NRS) and total nasal symptom score (TNSS) were recorded. Peff\u2010mCD4 cells were quantified as CD154\n +<\/jats:sup>\n CD137\n +<\/jats:sup>\n cells within memory CD4\n +<\/jats:sup>\n T cells after short\u2010term ex\u00a0vivo allergen stimulation.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Peff\u2010mCD4 frequency was strongly associated with NRS and TNSS in both the HDM\u2010specific (Spearman\n \u03c1<\/jats:italic>\n \u2009=\u20090.882 and 0.835, respectively) and JCP\u2010specific analyses (\n \u03c1<\/jats:italic>\n \u2009=\u20090.828 and 0.769, respectively; all\n q<\/jats:italic>\n \u2009<\u20090.001). In contrast, sIgE showed weaker associations with symptom scores, and none of the four sIgE\u2013symptom associations remained significant after FDR adjustment. These peff\u2010mCD4 associations remained significant after adjustment for age and sex. In exploratory ROC analyses using TNSS \u22658 as an operational threshold, peff\u2010mCD4 yielded AUCs of 0.867 for HDM and 0.910 for JCP.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Peff\u2010mCD4 frequency was strongly associated with symptom burden in pediatric AR. Larger longitudinal and externally validated studies are required to determine its potential utility as a peripheral blood cellular correlate of clinical symptom burden.<\/jats:p>\n \n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/pai.70509","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:41:20Z","timestamp":1792064480000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Peripheral effector\u2010memory\n CD4<\/scp>\n +<\/sup>\n T cells reflect clinical symptom burden in pediatric allergic rhinitis"],"prefix":"10.1111","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1751-0555","authenticated-orcid":false,"given":"Takeshi","family":"Yamamoto","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine Chiba University Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7592-6352","authenticated-orcid":false,"given":"Eri","family":"Hayata","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine Chiba University Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terumi","family":"Ikarashi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine Chiba University Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruna","family":"Tokitomo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine Chiba University Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine Chiba University Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azusa","family":"Hiraoka","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine Chiba University Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9016-1274","authenticated-orcid":false,"given":"Kenta","family":"Zushi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine Chiba University Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine Chiba University Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6944-6161","authenticated-orcid":false,"given":"Toshiyuki","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine Chiba University Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7499-1204","authenticated-orcid":false,"given":"Taiji","family":"Nakano","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine Chiba University Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromichi","family":"Hamada","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine Chiba University Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"issue":"6","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.waojou.2026.101396","article-title":"Trends in the prevalence of childhood allergic diseases in Japan: comparison of surveys conducted in 1982, 1992, 2002, 2012, and 2022 (WJSAAC phase 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K","year":"2021","journal-title":"Mediat Inflamm"},{"issue":"4","key":"e_1_2_11_12_1","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.jaci.2022.06.024","article-title":"Single\u2010cell immunoprofiling after immunotherapy for allergic rhinitis reveals functional suppression of pathogenic TH2 cells and clonal conversion","volume":"150","author":"Iinuma T","year":"2022","journal-title":"J Allergy Clin Immunol"},{"issue":"401","key":"e_1_2_11_13_1","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aam9171","article-title":"A phenotypically and functionally distinct human TH2 cell subpopulation is associated with allergic disorders","volume":"9","author":"Wambre E","year":"2017","journal-title":"Sci Transl Med"},{"issue":"48","key":"e_1_2_11_14_1","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.aba6087","article-title":"Single\u2010cell transcriptomic analysis of allergen\u2010specific T cells in allergy and asthma","volume":"5","author":"Seumois G","year":"2020","journal-title":"Sci Immunol"},{"issue":"2","key":"e_1_2_11_15_1","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/j.1365-2222.2010.03641.x","article-title":"Distinct characteristics of seasonal (bet v 1) vs perennial (Der p 1\/Der p 2) allergen\u2010specific CD4+ T cell responses","volume":"41","author":"Wambre E","year":"2011","journal-title":"Clin Exp Allergy"},{"issue":"1","key":"e_1_2_11_16_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-025-01538-6","article-title":"Single\u2010cell RNA sequencing reveals immunological link between house dust mite allergy and childhood asthma","volume":"15","author":"Zou L","year":"2025","journal-title":"Sci Rep"},{"issue":"5","key":"e_1_2_11_17_1","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1016\/j.jaci.2017.09.041","article-title":"Synchronous immune alterations mirror clinical response during allergen immunotherapy","volume":"141","author":"Renand A","year":"2018","journal-title":"J Allergy 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