Notch ligands potentiate IL-7-driven proliferation and survival of human thymocyte precursors

Maymouna Magri, Ahmad Yatim, Clarisse Benne, Michèle Balbo, Adeline Henry, Alain Serraf, Seiji Sakano, Louis Gazzolo, Yves Lévy, Jean Daniel Lelièvre

Research output: Contribution to journalArticlepeer-review

Abstract

Notch and IL-7 are both well-characterized factors involved in T-cell development. In contrast to the mouse model, their precise requirements in the differentiation and/or proliferation of various stages of human thymic development have not been fully explored. Here, we demonstrate that IL-7 alone is sufficient to induce the differentiation of ex vivo purified CD34+ triple negative (TN) surface (s) CD3- CD4-CD8- (CD3-CD4-CD8-), CD4 immature single positive (ISP) (sCD3-CD4+CD8-) and double positive (DP) (sCD3-CD4+ CD8+) human thymic precursors to mature DP expressing sCD3 (sCD3+CD4+CD8+). We show that activation of Notch signaling by its ligands Delta-1 or Delta-4 potentiates IL-7-driven proliferation and survival of CD34+ TN and to a lesser extent of CD4+ ISP precursors. This effect of Notch is related to a sustained induction of IL-7 receptor α chain expression on thymocytes through a decreased methylation of its gene promoter. Thus, we show here that proliferation and differentiation of T-cell precursors are differentially modulated by IL-7 depending on the presence or absence of external signals. These results may have important implications for the clinical use of this cytokine as a strategy aimed at improving immune restoration.

Original languageEnglish
Pages (from-to)1231-1240
Number of pages10
JournalEuropean Journal of Immunology
Volume39
Issue number5
DOIs
StatePublished - May 2009
Externally publishedYes

Keywords

  • Delta 1
  • Delta 4
  • IL-7
  • IL-7 receptor
  • Notch

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