[PDF][PDF] Notch1 regulates maturation of CD4+ and CD8+ thymocytes by modulating TCR signal strength
DJ Izon, JA Punt, L Xu, FG Karnell, D Allman… - Immunity, 2001 - cell.com
DJ Izon, JA Punt, L Xu, FG Karnell, D Allman, PS Myung, NJ Boerth, JC Pui, GA Koretzky…
Immunity, 2001•cell.comNotch signaling regulates cell fate decisions in multiple lineages. We demonstrate in this
report that retroviral expression of activated Notch1 in mouse thymocytes abrogates
differentiation of immature CD4+ CD8+ thymocytes into both CD4 and CD8 mature single-
positive T cells. The ability of Notch1 to inhibit T cell development was observed in vitro and
in vivo with both normal and TCR transgenic thymocytes. Notch1-mediated developmental
arrest was dose dependent and was associated with impaired thymocyte responses to TCR …
report that retroviral expression of activated Notch1 in mouse thymocytes abrogates
differentiation of immature CD4+ CD8+ thymocytes into both CD4 and CD8 mature single-
positive T cells. The ability of Notch1 to inhibit T cell development was observed in vitro and
in vivo with both normal and TCR transgenic thymocytes. Notch1-mediated developmental
arrest was dose dependent and was associated with impaired thymocyte responses to TCR …
Abstract
Notch signaling regulates cell fate decisions in multiple lineages. We demonstrate in this report that retroviral expression of activated Notch1 in mouse thymocytes abrogates differentiation of immature CD4+CD8+ thymocytes into both CD4 and CD8 mature single-positive T cells. The ability of Notch1 to inhibit T cell development was observed in vitro and in vivo with both normal and TCR transgenic thymocytes. Notch1-mediated developmental arrest was dose dependent and was associated with impaired thymocyte responses to TCR stimulation. Notch1 also inhibited TCR-mediated signaling in Jurkat T cells. These data indicate that constitutively active Notch1 abrogates CD4+ and CD8+ maturation by interfering with TCR signal strength and provide an explanation for the physiological regulation of Notch expression during thymocyte development.
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