{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:57:18Z","timestamp":1791424638475,"version":"4.3.3"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2014,6,1]],"date-time":"2014-06-01T00:00:00Z","timestamp":1401580800000},"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":[[2014,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Naive CD4+ T cells require signals from the TCR and CD28 to produce IL-2, expand, and differentiate. However, these same signals are not sufficient to induce autocrine IL-2 production by naive CD8+ T cells, which require cytokines provided by other cell types to drive their differentiation. The basis for failed autocrine IL-2 production by activated CD8+ cells is unclear. We find that Ikaros, a transcriptional repressor that silences IL-2 in anergic CD4+ T cells, also restricts autocrine IL-2 production by CD8+ T cells. We find that CD8+ T cell activation in vitro in the absence of exogenous cytokines and CD4 help leads to marked induction of Ikaros, a known repressor of the Il2 gene. Naive murine CD8 T cells haplo-insufficient for Ikzf1 failed to upregulate Ikaros, produced autocrine IL-2, and differentiated in an IL-2\u2013dependent manner into IFN-\u03b3\u2013producing CTLs in response to TCR\/CD28 stimulation alone. Furthermore, Ikzf1 haplo-insufficient CD8+ T cells were more effective at controlling Listeria infection and B16 melanoma growth in vivo, and they could provide help to neighboring, non-IL-2\u2013producing cells to differentiate into IFN-\u03b3\u2013producing effectors. Therefore, by repressing autocrine IL-2 production, Ikaros ensures that naive CD8+ T cells remain dependent on licensing by APCs and CD4+ T cells, and it may therefore act as a cell-intrinsic safeguard against inappropriate CTL differentiation and immunopathology.<\/jats:p>","DOI":"10.4049\/jimmunol.1301992","type":"journal-article","created":{"date-parts":[[2014,4,29]],"date-time":"2014-04-29T07:24:55Z","timestamp":1398756295000},"page":"5118-5129","source":"Crossref","is-referenced-by-count":53,"title":["Ikaros Imposes a Barrier to CD8+ T Cell Differentiation by Restricting Autocrine IL-2 Production"],"prefix":"10.1093","volume":"192","author":[{"given":"Shaun","family":"O\u2019Brien","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajan M","family":"Thomas","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Philadelphia Research Institute , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald B","family":"Wertheim","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104"},{"name":"Children\u2019s Hospital of Philadelphia Research Institute , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuqin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D","family":"Wells","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104"},{"name":"Children\u2019s Hospital of Philadelphia Research Institute , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,6,1]]},"reference":[{"key":"2025032404324591500_r1","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1146\/annurev.immunol.26.021607.090357","article-title":"The biology of interleukin-2","volume":"26","author":"Malek","year":"2008","journal-title":"Annu. 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