{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:02:42Z","timestamp":1790935362180,"version":"4.1.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2009,2,1]],"date-time":"2009-02-01T00:00:00Z","timestamp":1233446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Forkhead box p3 (FOXP3) is known to program the acquisition of suppressive capacities in CD4+ regulatory T cells (Treg), whereas its role in CD8+ T cells is unknown. The current study investigates whether FOXP3 also acts as a Treg master switch in peripheral blood and tonsillar CD8+ T cells. Single-cell analyses reveal the existence of a FOXP3+CD8+ population in human tonsils, whereas FOXP3+CD8+ T cells are rarely detected in peripheral blood. Tonsillar FOXP3+CD8+ T cells exhibit a Treg phenotype with high CTLA-4 and CD45RO and low CD127 and CD69 expression. Interestingly, the tonsillar FOXP3+CD8+ T cells are mostly CD25negative and some cells also express the proinflammatory cytokines TNF-\u03b1, IFN-\u03b3, or IL-17A. Particularly, IL-17A-expressing cells are present among FOXP3+CD8+ T cells. Even though FOXP3 expression is at the detection limit in peripheral blood CD8+ T cells ex vivo, it can be induced in vitro in naive CD8+ T cells by polyclonal stimulation. The induced FOXP3+CD8+ T cells are predominantly CD25high and CD28high and similar to tonsillar cells, they produce high levels of TNF-\u03b1, IFN-\u03b3, and granzyme B. However, IL-4 expression is mutually exclusive and IL-17A expression is not detectable. These FOXP3+CD8+ T cells suppress the proliferation of CD4+ T cells in cocultures, while showing no direct cytotoxic activity. In conclusion, the current study characterizes FOXP3-expressing CD8+ T cells from human tonsils and shows that in vitro activation leads to FOXP3 expression in CD8+ T cells and gain of suppressive activity.<\/jats:p>","DOI":"10.4049\/jimmunol.0802271","type":"journal-article","created":{"date-parts":[[2009,2,9]],"date-time":"2009-02-09T12:02:33Z","timestamp":1234180953000},"page":"2124-2130","source":"Crossref","is-referenced-by-count":68,"title":["Unique Phenotype of Human Tonsillar and In Vitro-Induced FOXP3+CD8+ T Cells"],"prefix":"10.1093","volume":"182","author":[{"given":"Kerstin","family":"Siegmund","sequence":"first","affiliation":[{"name":"Swiss Institute of Allergy and Asthma Research, University of Zurich , Davos,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"R\u00fcckert","sequence":"additional","affiliation":[{"name":"Swiss Institute of Allergy and Asthma Research, University of Zurich , Davos,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Ouaked","sequence":"additional","affiliation":[{"name":"Swiss Institute of Allergy and Asthma Research, University of Zurich , Davos,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"B\u00fcrgler","sequence":"additional","affiliation":[{"name":"Swiss Institute of Allergy and Asthma Research, University of Zurich , Davos,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Speiser","sequence":"additional","affiliation":[{"name":"Spital Davos, Otorhinolaryngology Department , Davos,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cezmi A","family":"Akdis","sequence":"additional","affiliation":[{"name":"Swiss Institute of Allergy and Asthma Research, University of Zurich , Davos,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten B","family":"Schmidt-Weber","sequence":"additional","affiliation":[{"name":"Allergy and Clinical Immunology, National Heart & Lung Institute, Imperial College London , London,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,2,15]]},"reference":[{"key":"2026012806245810100_R1","first-page":"937","article-title":"CD8+CD122+ regulatory T cells recognize activated T cells via conventional MHC class I-\u03b1\u03b2TCR interaction and become IL-10-producing active regulatory cells.","volume-title":"Int. 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