Figure 5
Figure 5. Posttransplantation bortezomib therapy enhances GVT in the absence of donor CD4+ T cells and is dependent on IFNγ production from donor CD8+ T cells. (A) BALB/c (H2d) mice received 3 × 105 A20 cells on day 6. On day 0, BALB/c (H2d) mice received 10 million FvB (H2q) bone marrow with or without 1 million unfractionated splenocytes or CD4 in vivo–depleted splenocytes. Mice received PBS or 7.5 μg/dose bortezomib on days 0, +6, +11, and +16 after BMT (n = 7-11 mice/group) and were monitored for survival. Representative data from 1 of 2 independent experiments are presented. (B) BALB/c (H2d) mice received 3 × 105 A20 cells on day 6. On day 0, BALB/c (H2d) mice received 10 million B6 (H2b) bone marrow with/without 4 × 105 Ifnγ+/+ or Ifnγ−/− CD8+ T cells followed by 7.5 μg/dose bortezomib on days 0, +6, +11, and +16 after BMT (n = 8-9 mice/group). Representative data from 1 of 3 independent experiments are presented. Prolonged bortezomib therapy after allogeneic BMT result in significant decreases in survival in the mice that received Ifnγ−/− CD8+ T cells compared with mice that received Ifnγ+/+ CD8+ T cells (P < .005; log rank test).

Posttransplantation bortezomib therapy enhances GVT in the absence of donor CD4+ T cells and is dependent on IFNγ production from donor CD8+ T cells. (A) BALB/c (H2d) mice received 3 × 105 A20 cells on day 6. On day 0, BALB/c (H2d) mice received 10 million FvB (H2q) bone marrow with or without 1 million unfractionated splenocytes or CD4 in vivo–depleted splenocytes. Mice received PBS or 7.5 μg/dose bortezomib on days 0, +6, +11, and +16 after BMT (n = 7-11 mice/group) and were monitored for survival. Representative data from 1 of 2 independent experiments are presented. (B) BALB/c (H2d) mice received 3 × 105 A20 cells on day 6. On day 0, BALB/c (H2d) mice received 10 million B6 (H2b) bone marrow with/without 4 × 105Ifnγ+/+ or Ifnγ−/− CD8+ T cells followed by 7.5 μg/dose bortezomib on days 0, +6, +11, and +16 after BMT (n = 8-9 mice/group). Representative data from 1 of 3 independent experiments are presented. Prolonged bortezomib therapy after allogeneic BMT result in significant decreases in survival in the mice that received Ifnγ−/− CD8+ T cells compared with mice that received Ifnγ+/+ CD8+ T cells (P < .005; log rank test).

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