OCCURRENCE OF A SILENCER OF THE INTERLEUKIN-2 GENE IN NAIVE BUT NOT IN MEMORY RESTING T-HELPER LYMPHOCYTES

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 rep ertoire and maintenance of self-tolerance. In the present study, analy sis 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) r egulate IL-2 transcription by a mechanism involving both a silencer an d 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 transiti on from inactive to active functional state of a positive transcriptio n factor binding to these promoter elements as well as its cytoplasmic or nuclear location: in resting memory T cells the activator is locat ed 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 fac tor changes irreversibly after the first encounter of T cells with ant igen. It is most likely that the presence of a silencer contributes to the more stringent activation requirements of naive CD4+ T cells.