Publications (2)10.21 Total impact
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Article: Notch ligands potentiate IL-7-driven proliferation and survival of human thymocyte precursors.
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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 alpha 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.European Journal of Immunology 05/2009; 39(5):1231-40. · 5.10 Impact Factor -
Article: Notch ligands potentiate IL‐7‐driven proliferation and survival of human thymocyte precursors
[show abstract] [hide abstract]
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.European Journal of Immunology 04/2009; 39(5):1231 - 1240. · 5.10 Impact Factor