Figure 2
Figure 2. ABT-737 reverses the antitolerogenic effect of CsA. B6 recipients (H-2b) were treated with a conditioning protocol including TBI (1.5 Gy), MR1 (2 mg), and 25 × 106 fully MHC-mismatched BM cells from CBA donors (H-2k). Six weeks after BMT, skin transplantation from CBA and BALB/c (3rd party, H-2d) donors was performed. (A) CsA (10 mg/kg/day, from day −3 to day 12 after BMT) had a deleterious impact on mixed chimerism induction, but this effect was reversed in combination with ABT-737 (ABT, 50 mg/kg/day, from day −3 to day 12 after BMT), as shown in the level of chimerism in different hematopoietic cell lineages in peripheral blood leukocytes (20 weeks after BMT). Notably, the chimerism level in the combination group was even higher than in the group treated with ABT-737 alone. **P < .01; ***P < .001; N = 7-8. (B) Most recipients receiving CsA alone rejected CBA skin grafts, whereas all mice treated with a combination of CsA and ABT-737 accepted CBA and promptly rejected BALB/c skin grafts. N = 7-8/group.

ABT-737 reverses the antitolerogenic effect of CsA. B6 recipients (H-2b) were treated with a conditioning protocol including TBI (1.5 Gy), MR1 (2 mg), and 25 × 106 fully MHC-mismatched BM cells from CBA donors (H-2k). Six weeks after BMT, skin transplantation from CBA and BALB/c (3rd party, H-2d) donors was performed. (A) CsA (10 mg/kg/day, from day −3 to day 12 after BMT) had a deleterious impact on mixed chimerism induction, but this effect was reversed in combination with ABT-737 (ABT, 50 mg/kg/day, from day −3 to day 12 after BMT), as shown in the level of chimerism in different hematopoietic cell lineages in peripheral blood leukocytes (20 weeks after BMT). Notably, the chimerism level in the combination group was even higher than in the group treated with ABT-737 alone. **P < .01; ***P < .001; N = 7-8. (B) Most recipients receiving CsA alone rejected CBA skin grafts, whereas all mice treated with a combination of CsA and ABT-737 accepted CBA and promptly rejected BALB/c skin grafts. N = 7-8/group.

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