Fas ligand (FasL/CD95L/APO-1L) is one of a growing number of TNF family mem
bers whose triggering costimulates maximal proliferation of activated T cel
ls. In this study we show that maximal Ag-dependent accumulation of transfe
rred TCR-transgenic CD8+ T cells requires Fas (CD95/APO-1) expression by th
e adoptive hosts. Additionally, adoptively transferred FasL(+) CD8(+) T cel
ls demonstrate a 2-fold advantage in Ag-driven expansion over their Fast-co
unterparts. This study illustrates the in vivo role of TCR-dependent FasL c
ostimulation In the Ag-specific proliferation of both heterogeneous and hom
ogeneous populations of primary CD8+ T cells and long-term CTL lines. Thus,
cross-linking FasL, on naive and Ag-experienced CD8+ T cells whose Ag-spec
ific TCRs are engaged is required to drive maximal cellular proliferation i
n vivo.