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Occurrence of a silencer of the interleukin‐2 gene in naive but not in memory resting T helper lymphocytes
Author(s) -
Mouzaki Athanasia,
Rungger Duri,
Tucci Alessandra,
Doucet Arlette,
Zubler Rudolf H.
Publication year - 1993
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830230711
Subject(s) - biology , t cell , interleukin 21 , silencer , microbiology and biotechnology , antigen presenting cell , cytotoxic t cell , t helper cell , transcription factor , cd28 , antigen , immune system , immunology , gene , in vitro , genetics , mechanical engineering , engineering , inlet
Abstract 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.