Fas ligand costimulates the in vivo proliferation of CD8+ T cells

Fas ligand (FasL/CD95L/APO-1L) is one of a growing number of TNF family members whose triggering costimulates maximal proliferation of activated T cells. In this study we show that maximal Ag-dependent accumulation of transferred TCR-transgenic CD8+ T cells requires Fas (CD95/APO-1) expression by the adoptive hosts. Additionally, adoptively transferred FasL(+) CD8(+) T cells demonstrate a 2-fold advantage in Ag-driven expansion over their Fast-counterparts. This study illustrates the in vivo role of TCR-dependent FasL costimulation In the Ag-specific proliferation of both heterogeneous and homogeneous 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-specific TCRs are engaged is required to drive maximal cellular proliferation in vivo.