Notch1 signaling promotes the maturation of CD4 and CD8 SP thymocytes

Immunity. 2000 Jul;13(1):73-84. doi: 10.1016/s1074-7613(00)00009-1.

Abstract

Notch proteins regulate many developmental processes. Notch1 is highly expressed on thymocytes, but its role in regulating their development is not known. We show that activation of Notch1 signaling in CD4+CD8+ double positive thymocytes promotes the maturation of both CD4+ and CD8+ single positive thymocytes and that this occurs in the absence of interactions between the T cell receptor and MHC molecules expressed on thymic epithelial cells. We have also identified several genes that are transcriptionally regulated by Notch1 in T cells and show that they are upregulated during maturation into both single positive lineages. These observations suggest that Notch1 signaling plays a role in promoting maturation into both the CD4 and CD8 T cell lineages.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ADAM Proteins
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Carrier Proteins*
  • Disintegrins*
  • Epithelial Cells
  • Homeodomain Proteins / genetics
  • Hyaluronan Receptors / biosynthesis
  • Hypoxanthine Phosphoribosyltransferase / genetics
  • Leukopoiesis*
  • Major Histocompatibility Complex
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Metalloendopeptidases*
  • Metalloproteases*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Muscle Proteins / genetics
  • Nuclear Proteins / genetics
  • Phosphoproteins / genetics
  • Proteins / genetics
  • Receptor, Notch1
  • Receptors, Cell Surface*
  • Receptors, Interleukin-2 / biosynthesis
  • Signal Transduction*
  • Transcription Factor HES-1
  • Transcription Factors*
  • Up-Regulation

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Carrier Proteins
  • Disintegrins
  • Hes1 protein, mouse
  • Homeodomain Proteins
  • Hyaluronan Receptors
  • Ifi16 protein, mouse
  • Membrane Proteins
  • Muscle Proteins
  • Notch1 protein, mouse
  • Nuclear Proteins
  • Phosphoproteins
  • Proteins
  • Receptor, Notch1
  • Receptors, Cell Surface
  • Receptors, Interleukin-2
  • Transcription Factor HES-1
  • Transcription Factors
  • deltex protein, vertebrate
  • Hypoxanthine Phosphoribosyltransferase
  • Metalloproteases
  • ADAM Proteins
  • ADAM19 protein, human
  • Adam19 protein, mouse
  • Metalloendopeptidases