Human LAP(+)GARP(+)FOXP3(+) regulatory T cells attenuate xenogeneic graft versus host disease

Wang, Huihui; Song, Hyo; Pham, Anha V.; Cooper, Laurence J.; Schulze, Janika J.; Olek, Sven; Tran, Dat Q.

To determine whether expanded LAP + Tregs are effective in suppressing human CD25-depleted PBMC-induced xenogeneic GVHD, we used a xenogeneic model of GVHD in which Tregs are co-transferred at a 1:1 ratio with allogeneic CD25-depleted PBMC (30 × 10 6 each) into NSG recipients to compare the potency and safety of in vitro-expanded LAP + Tregs and LAP − cells ( Figure 6C ). CD25 − PBMC administered alone results in a median survival of 32 days. The co-transfer of LAP parent (CD25 + ) or LAP + Tregs increased median survival to 39 (p < 0.05) and 47 days (p < 0.001), respectively. The LAP − nonTregs showed similar median survival (31 days) with PBMC group. The survival of LAP + group was significantly higher than LAP − group (p < 0.001). Compared with CD25 + group, LAP + Tregs increased median survival from 39 to 47 days. However, no statistic different was found, since some of the CD25 + parent populations have less contaminating nonTregs and therefore higher level of FOXP3 + Tregs ( Figure 2D, 5B) . Average body weight (% of initial weight) for mice surviving on given day for different groups was shown in Figure S3 .