SURFACE MOLECULES THAT DRIVE T-CELL DEVELOPMENT IN-VITRO IN THE ABSENCE OF THYMIC EPITHELIUM AND IN THE ABSENCE OF LINEAGE-SPECIFIC SIGNALS

Differentiation of immature double positive (DP) CD4(+) CD8(+). thymoc ytes into single positive (SP) CD4(+) and CD8(+) T cells is referred t o as positive selection and requires physical contact with thymic cort ical epithelium. We now have identified ''coinducer'' molecules on DP thymocytes that, together with TCR, signal DP thymocytes to differenti ate into SP T cells in vitro in the absence of thymic epithelium. A re markable number of different molecules on DP thymocytes possessed ''co inducing'' activity, including CD2, CD5, CD24, CD28, CD49d, CD81, and TSA-1. Interestingly, in vitro differentiation occurred in the absence of lineage-specific signals, yet resulted in the selective generation of CD4(+)CD8(-) T cells. Thus, the present study has identified surfa ce molecules that can signal DP thymocytes to differentiate into SP T cells in the absence of thymic epithelium and has characterized a defa ult pathway for CD4(+) T cell differentiation.