Occurrence of a silencer of the interleukin-2 gene in naive but not in memory resting T helper lymphocytes

Article Article scientifique Article Occurrence of a silencer of the interleukin-2 gene in naive but not in memory resting T helper lymphocytes eng 1993-07 author Mouzaki Athanasia 24222 author Rungger Duri 25122 author Tucci-Cherubini Alessandra 24321 author Doucet Arlette author Zubler Rudolf 24774 1469-1474 10.1002/eji.1830230711 8325322 0014-2980 https://onlinelibrary.wiley.com/doi/10.1002/eji.1830230711 In the immune system the first activation of a naive T cell by antigen is a key step in the shaping of the peripheral T cell specificity repertoire and maintenance of self-tolerance. In the present study, analysis of the interleukin-2 (IL-2) gene activation shows that naive human helper T cells (cord blood CD4+ T cells, adult CD4+CD45RO− T cells) regulate IL-2 transcription by a mechanism involving both a silencer and an activator acting on the purine-rich IL-2 promoter elements (NF-AT binding sites). By contrast, memory cells, either in vitro activated helper T cells reverting to a resting state, or CD4+ T (memory) clones, or CD4+CD45RO+ T cells isolated ex vivo, no longer have a silencer. Their IL-2 transcription seems to be controlled solely by the transition from inactive to active functional state of a positive transcription factor binding to these promoter elements as well as its cytoplasmic or nuclear location: in resting memory T cells the activator is located in the cytoplasm and is inactive, whereas in stimulated cells it is functional in promoting transcription and now resides in the nucleus. Thus, the regulation of the gene coding for the main T cell growth factor changes irreversibly after the first encounter of T cells with antigen. It is most likely that the presence of a silencer contributes to the more stringent activation requirements of naive CD4+ T cells. Interleukin-2 Gene regulation Transcription factors Dewey 616 Dewey 590 Swiss National Science Foundation 31.33437.92 Swiss National Science Foundation 3.128654.90 Fondation pour la recherche hematologique, Geneva 44 Département de génétique et évolution 162 56 Département de médecine 221 false European Journal of Immunology 23 7 c66f02e2-0588-4f3e-b08b-8089a554c0f7 Article (Published version) Restricted Mouzaki_EJI-1993231469.pdf 4400024 application/pdf restrictedAccess Faculté des sciences / Section de biologie / Département de génétique et évolution Faculté de médecine / Section de médecine clinique / Département de médecine

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Occurrence of a silencer of the interleukin-2 gene in naive but not in memory resting T helper lymphocytes	European Journal of Immunology			1993	142	0

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Tucci-Cherubini, Alessandra