An activated form of Notch influences the choice between CD4 and CD8 T cell lineages.
Notch is a transmembrane receptor that controls cell fate decisions in Drosophila and whose role in mammalian cell fate decisions is beginning to be explored. We are investigating the role of Notch in a well-studied mammalian cell fate decision: the choice between the CD8 and CD4 T cell lineages. Here we report that expression of an activated form of Notch1 in developing T cells of the mouse leads to both an increase in CD8 lineage T cells and a decrease in CD4 lineage T cells. Expression of activated Notch permits the development of mature CD8 lineage thymocytes even in the absence of class I major histocompatability complex (MHC) proteins, ligands that are normally required for the development of these cells. However, activated Notch is not sufficient to promote CD8 cell development when both class I and class II MHC are absent. These results implicate Notch as a participant in the CD4 versus CD8 lineage decision.
Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
E
E
Robey
D
D
Chang
A
A
Itano
D
D
Cado
H
H
Alexander
D
D
Lans
G
G
Weinmaster
P
P
Salmon
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D006183:H-2 Antigens / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011828:Radiation Chimera; D051880:Receptors, Notch; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics
D006183:H-2 Antigens; D008565:Membrane Proteins; D051880:Receptors, Notch; D011993:Recombinant Fusion Proteins; D001613:beta 2-Microglobulin