Figure 7.
CD8+Bim−/−Tregs are more potent than wild-type CD8+Tregs for the suppression of lethal GVHD. Irradiated Balb/c mice were transplanted with 8 × 106 B6.PL (Thy1.1+) BM together with spleen cells (adjusted to yield a dose of 0.6 × 106 αβ T cells). Animals also received either 0.6 × 106 in vitro-differentiated alloantigen-induced CD8+ Thy1.2+ Tregs from FoxpEGFP (red circles, n = 10) or Bim−/− Foxp3EGFP (blue boxes, n = 10) mice. (A) Representative contour plots depicting the percentage of H-2Kb+ Thy1.2+ Tregs 10 days posttransplantation. (B) The percentage of CD8+ Tregs that maintained Foxp3 expression and the absolute number of CD8+ Foxp3+ T cells in the spleen, liver, lung, and colon of mice reconstituted with adoptively transferred CD8+ FoxpEGFP or CD8+ Bim−/− Foxp3EGFP Tregs cells. Data are from 2 experiments. (C) Lethally irradiated Balb/c mice were transplanted with B6 BM alone (red circle, n = 12) or together with B6 spleen cells. Cohorts of animals reconstituted with B6 BM and spleen cells then received either no additional cells (blue squares, n = 20) or in vitro-differentiated alloantigen-induced CD8+ Tregs from B6 FoxpEGFP (purple triangles, n = 19) or Bim−/− Foxp3EGFP (green triangles, n = 19) mice at a 1:1 ratio. Overall survival is depicted. Data are the cumulative results from 4 experiments. *P < .05; **P < .01; ***P < .001.