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 beginni ng to be explored. We are investigating the role of Notch in a well-st udied 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. Express ion of activated Notch permits the development of mature CD8 lineage t hymocytes even in the absence of class I major histocompatability comp lex (MHC) proteins, ligands that are normally required for the develop ment of these cells. However, activated Notch is not sufficient to pro mote CD8 cell development when both class I and class II MHC are absen t. These results implicate Notch as a participant in the CD4 versus CD 8 lineage decision.