Notch1 signaling promotes the maturation of CD4 and CD8 SP thymocytes.
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.
Department of Immunology and Howard Hughes Medical Institute, University of Washington, Seattle 98195, USA.
M L
ML
Deftos
E
E
Huang
E W
EW
Ojala
K A
KA
Forbush
M J
MJ
Bevan
D051722:ADAM Proteins; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002352:Carrier Proteins; D019483:Disintegrins; D004847:Epithelial Cells; D018398:Homeodomain Proteins / Q000235:genetics; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D019891:Leukopoiesis; D008285:Major Histocompatibility Complex; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008666:Metalloendopeptidases; D045726:Metalloproteases; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009124:Muscle Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D011506:Proteins / Q000235:genetics; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D015398:Signal Transduction; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; D015854:Up-Regulation
D051722:ADAM Proteins; D051792:Basic Helix-Loop-Helix Proteins; D002352:Carrier Proteins; D019483:Disintegrins; D018398:Homeodomain Proteins; D018960:Hyaluronan Receptors; D007041:Hypoxanthine Phosphoribosyltransferase; D008565:Membrane Proteins; D008666:Metalloendopeptidases; D045726:Metalloproteases; D009124:Muscle Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D015375:Receptors, Interleukin-2; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; C489734:Hes1 protein, mouse; C489664:Ifi16 protein, mouse; C497762:Notch1 protein, mouse; C409218:deltex protein, vertebrate; C411902:ADAM19 protein, human; C096116:Adam19 protein, mouse