Transient display of SA-FasL protein on human PBMCs is effective in preventing xenogeneic aGVHD. (A) Absolute number of human cells recovered from NSG recipients. NSG mice were subjected to 200 cGy total body irradiation followed by IV infusion of neutrophil-depleted human PBMCs (5 × 106) engineered with SA-FasL (25 ng/106 cells) or equimolar of SA protein as control. Splenocytes and liver infiltrates harvested 5 days after infusion were analyzed using flow cytometry gating on total human cells (CD45+), CD4+, or CD8+ T cells. Data were pooled from 3 independent experiments. (B) Prevention of xenogeneic aGVHD using SA-FasL–engineered PBMC. Irradiated NSG mice underwent transplantation with 10 × 106 human PBMCs left unmodified or engineered with SA or the indicated doses of SA-FasL. Animals were monitored for the signs and development of xenogeneic aGVHD. For comparison of means, unpaired two-tailed t test was used in panel A. Survival curve comparison was done by using log-rank (Mantel Cox). Data are represented as mean ± SEM. SEM, standard error mean. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001.
