{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T19:41:06Z","timestamp":1776627666244,"version":"3.51.2"},"reference-count":5,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T00:00:00Z","timestamp":1776556800000},"content-version":"vor","delay-in-days":18,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Penn State Department of Anesthesiology and Perioperative Medicine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Functional T-cell assays such as the IFN-\u03b3 ELISpot are increasingly used for immune phenotyping in infection, cancer, and critical illness. Many studies, including recent work linking low IFN-\u03b3 ELISpot responses to adverse outcomes in sepsis, compare patient samples to a single cross-sectional healthy donor baseline, implicitly assuming temporal stability of IFN-\u03b3 secretion in health. We conducted a longitudinal study of 9 healthy adults using whole-blood anti-CD3\/anti-CD28 ELISpot assays with and without IL-7 co-stimulation. Absolute IFN-\u03b3 production varied significantly within individuals over approximately 10\u2009weeks, whereas the ratio of IL-7\u2013augmented to anti-CD3\/anti-CD28\u2013only responses remained remarkably stable across all readouts. This IL-7 responsiveness ratio may represent a robust, time-independent functional metric of intact T-cell signaling. These findings demonstrate that absolute IFN-\u03b3 ELISpot values in healthy individuals are dynamic and support ratio-based metrics for immune phenotyping applications.<\/jats:p>","DOI":"10.1093\/immhor\/vlag021","type":"journal-article","created":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T19:01:09Z","timestamp":1776625269000},"source":"Crossref","is-referenced-by-count":0,"title":["Temporal variability in healthy donor IFN-\u03b3 ELISpot responses reveals a stable IL-7\u2013responsive functional metric for immune phenotyping"],"prefix":"10.1093","volume":"10","author":[{"given":"Annemarie","family":"Nguyen","sequence":"first","affiliation":[{"name":"Penn State College of Medicine , Hershey, PA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruth-Ann","family":"Brown","sequence":"additional","affiliation":[{"name":"Penn State College of Medicine , Hershey, PA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9596-001X","authenticated-orcid":false,"given":"Anthony S","family":"Bonavia","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, Division of Critical Care Medicine, Penn State Health , Hershey, PA,","place":["United States"]},{"name":"Critical Illness and Sepsis Research Center, Penn State College of Medicine , Hershey, PA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,4,19]]},"reference":[{"key":"2026041915010226900_vlag021-B1","doi-asserted-by":"crossref","first-page":"940030","DOI":"10.3389\/fimmu.2022.940030","article-title":"Comparison of rapid cytokine immunoassays for functional immune phenotyping","volume":"13","author":"Bonavia","year":"2022","journal-title":"Front Immunol"},{"key":"2026041915010226900_vlag021-B2","first-page":"e1106","article-title":"Predicting organ dysfunction in septic and critically ill patients: a prospective cohort study using rapid ex vivo immune profiling","volume":"6","author":"Samuelsen","year":"2024","journal-title":"Crit Care Explor"},{"key":"2026041915010226900_vlag021-B3","doi-asserted-by":"crossref","first-page":"e175785","DOI":"10.1172\/jci.insight.175785","article-title":"Adverse outcomes and an immunosuppressed endotype in septic patients with reduced IFN-\u03b3 ELISpot","volume":"9","author":"Barrios","year":"2024","journal-title":"JCI Insight"},{"key":"2026041915010226900_vlag021-B4","doi-asserted-by":"crossref","first-page":"23","DOI":"10.4049\/jimmunol.2001088","article-title":"A whole blood enzyme-linked immunospot assay for functional immune endotyping of septic patients","volume":"206","author":"Mazer","year":"2021","journal-title":"J Immunol"},{"key":"2026041915010226900_vlag021-B5","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.smim.2012.04.010","article-title":"IL-7 signaling and CD127 receptor regulation in the control of T cell homeostasis","volume":"24","author":"Carrette","year":"2012","journal-title":"Semin Immunol"}],"container-title":["ImmunoHorizons"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/immunohorizons\/article-pdf\/10\/4\/vlag021\/68112026\/vlag021.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/immunohorizons\/article-pdf\/10\/4\/vlag021\/68112026\/vlag021.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T19:01:10Z","timestamp":1776625270000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/immunohorizons\/article\/doi\/10.1093\/immhor\/vlag021\/8658906"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":5,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4,11]]}},"URL":"https:\/\/doi.org\/10.1093\/immhor\/vlag021","relation":{},"ISSN":["2573-7732"],"issn-type":[{"value":"2573-7732","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,4]]},"published":{"date-parts":[[2026,4]]},"article-number":"vlag021"}}