{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T17:28:23Z","timestamp":1775582903605,"version":"3.50.1"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":1741,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Iron uptake via the transferrin receptor (CD71) is a pivotal mechanism for T cell proliferation. Yet, it is incompletely understood if targeting of CD71 also affects the differentiation and functional polarization of primary human T cells. In this study, we demonstrate that inhibition of iron ingestion with blocking mAbs against CD71 induces nonproliferating T cells, which release high amounts of IL-2. Targeting of CD71 with blocking or nonblocking mAbs did not alter major signaling pathways and the activation of the transcription factors NF-\u03baB, NFAT, or AP-1 as analyzed in Jurkat T cells. Growth arrest in iron-deficient (Fe-def) T cells was prevented upon addition of exogenous iron in the form of ferric ammonium citrate but was not reversible by exogenous IL-2. Surprisingly, protein synthesis was found to be intact in Fe-def T cells as demonstrated by comparable levels of CD69 upregulation and cytokine production with iron-sufficient T cells upon stimulation with CD3 plus CD28 mAbs. Indeed, high amounts of IL-2 were detectable in the supernatant of Fe-def T cells, which was accompanied with a reduced cell surface expression of IL-2R. When we used such Fe-def T cells in allogeneic MLRs, we observed that these cells acquired an accessory cell function and stimulated the proliferation of bystander T cells by providing IL-2. Thus, the results of our study demonstrate that iron deprivation causes nonproliferating, altruistic T cells that can help and stimulate other immune cells by providing cytokines such as IL-2.<\/jats:p>","DOI":"10.4049\/immunohorizons.2000003","type":"journal-article","created":{"date-parts":[[2020,4,13]],"date-time":"2020-04-13T20:35:56Z","timestamp":1586810156000},"page":"165-177","source":"Crossref","is-referenced-by-count":29,"title":["Iron Deprivation in Human T Cells Induces Nonproliferating Accessory Helper Cells"],"prefix":"10.1093","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3246-2317","authenticated-orcid":false,"given":"Verena","family":"Berg","sequence":"first","affiliation":[{"name":"Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna , A-1090 Vienna ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0079-6777","authenticated-orcid":false,"given":"Madhura","family":"Modak","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna , A-1090 Vienna ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5191-9031","authenticated-orcid":false,"given":"Jennifer","family":"Brell","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna , A-1090 Vienna ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Puck","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna , A-1090 Vienna ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarojinidevi","family":"K\u00fcnig","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna , A-1090 Vienna ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"Jutz","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna , A-1090 Vienna ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6848-4097","authenticated-orcid":false,"given":"Peter","family":"Steinberger","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna , A-1090 Vienna ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7478-4173","authenticated-orcid":false,"given":"Gerhard J","family":"Zlabinger","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna , A-1090 Vienna ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3304-6975","authenticated-orcid":false,"given":"Johannes","family":"St\u00f6ckl","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna , A-1090 Vienna ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,4,13]]},"reference":[{"key":"2025010608421859200_r1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.tcb.2006.12.003","article-title":"Iron uptake and metabolism in the new millennium","volume":"17","author":"Dunn","year":"2007","journal-title":"Trends Cell Biol."},{"key":"2025010608421859200_r2","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.bbagen.2011.10.013","article-title":"Regulation of iron transport and the role of transferrin","volume":"1820","author":"Gkouvatsos","year":"2012","journal-title":"Biochim. 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