{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T21:51:12Z","timestamp":1784325072777,"version":"3.55.0"},"reference-count":12,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunol Cell Biol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The classical three\u2010signal model of na\u00efve T\u2010cell activation, including T\u2010cell receptor engagement, co\u2010stimulation, and cytokine support, has provided a durable conceptual framework for understanding adaptive immunity. Yet, this linear population model underestimates the spatial, temporal, and cooperative complexity governing individual T\u2010cell fate. Exponential technological advances in genomics approaches over the last decade, including single\u2010cell RNA\u2010sequencing, trajectory inference, and multimodal profiling, have enabled the resolution of cellular heterogeneity and developmental hierarchies at the single cell level. A series of studies published in 2025 demonstrate that CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell activation is not a singular event but an iterative developmental program distributed across anatomical niches and sequential signaling phases. Distinct waves of T\u2010cell priming refine clonal selection, where lymph nodes function as specialized hubs sustaining stem\u2010like progenitors during chronic infection and cancer, while tissue microenvironments provide late\u2010stage reinforcement or restraint, and noncanonical helper networks restore dysfunctional CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u00a0cells through local interactions. Collectively, these findings position T\u2010cell activation as a dynamic process shaped by spatial and anatomical organization and branched environmental cues. Mapping T\u2010cell activation one cell at a time has started to reveal a distributed network of developmental checkpoints, raising the prospect that future immunotherapies will target activation trajectories rather than simply triggering activation signals.\n                  <\/jats:p>","DOI":"10.1111\/imcb.70123","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T06:15:47Z","timestamp":1777011347000},"page":"569-573","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mapping T\u2010cell activation one cell at a time"],"prefix":"10.1111","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0704-1254","authenticated-orcid":false,"given":"Jessica G","family":"Borger","sequence":"first","affiliation":[{"name":"School of Translational Medicine Monash University  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2922-0379","authenticated-orcid":false,"given":"Megan F","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Medical Biology The University of Melbourne  Melbourne VIC Australia"},{"name":"The Walter and Eliza Hall Institute of Medical Research  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-024-01168-4"},{"key":"e_1_2_10_3_1","unstructured":"HuangC\u2010Y.Thymus a beginning and end2022 18 March 2026. Available from:https:\/\/www.nature.com\/articles\/d42859\u2010022\u201000034\u20105."},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202170126"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.02.006"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2006.00382.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.10.5165"},{"key":"e_1_2_10_8_1","volume-title":"Janeway's Immunobiology, 9th edn","author":"Murphy KaW C","year":"2017"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21197357"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adq1405"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-025-02276-7"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-025-02219-2"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-025-02199-3"}],"container-title":["Immunology &amp; Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imcb.70123","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/imcb.70123","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imcb.70123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T20:05:27Z","timestamp":1783109127000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imcb.70123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,23]]},"references-count":12,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1111\/imcb.70123"],"URL":"https:\/\/doi.org\/10.1111\/imcb.70123","archive":["Portico"],"relation":{},"ISSN":["0818-9641","1440-1711"],"issn-type":[{"value":"0818-9641","type":"print"},{"value":"1440-1711","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,23]]},"assertion":[{"value":"2026-04-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}