Both CD4+ and CD8+ T cells are sensitive to FasL costimulation. (A and B) Schematic diagram of the blocking assay for each cell type is presented above the appropriate panel of data. Soluble FasIgG (denoted by ∗) blocks both positive costimulatory and negative death signals by binding to FasL. The sizes of the arrows in each diagram correlate with the putative strength of each signal. (A) [3H]dT uptake by purified CD8+ T cells from B6.wt and B6.lpr mice cocultured with allogeneic H-2k stimulators alone or in the presence of soluble HuIgG or soluble FasIgG during the entire culture period. Ag-stimulated CD8+ T cells receive a positive signal through FasL and a weak negative signal through Fas, a result of their reduced sensitivity to Fas-mediated death. Only the positive signal is received by lpr CD8+ T cells. (B) [3H]dT uptake by purified CD4+ T cells from B6.wt and B6.lpr mice cocultured with H-2bm12 stimulators alone or in the presence of soluble HuIgG or soluble FasIgG during the entire culture period. For CD4+ T cells, the sensitivity to Fas-mediated death (indicated by the large arrow and the negative sign) may mask the positive signal delivered on the interaction of FasL and Fas. The negative signal is missing from lpr CD4+ T cells. (C) [3H]dT uptake by B6.wt, B6.lpr, and B6.gld CTL lines seeded over suboptimal amounts of plate-bound anti-CD3 with either plate-bound FasIgG or HuIgG. (D) Same as C using CD4+ T cell lines as responders. Experiments were repeated four times, and data are averages of triplicate wells with error bars representing the SD of the mean within each experiment. The ratios indicate the fold increase in proliferation of cultures in FasIgG-coated relative to HuIgG-coated wells.