Administration of bortezomib immediately before transplantation protects mice from lethal GVHD. Lethally irradiated (1000 cGy) B6 mice underwent transplantation with TCD B10.BR BM alone or together with B10.BR spleen cells adjusted to yield a dose of either 2 × 106 (A) or 4 × 106 T cells (B). Mice that received transplanted TCD BM only either were left untreated (□, n = 8) or were administered bortezomib (1 mg/kg, day 0) (○, n = 6) immediately before transplantation. Animals that received transplanted TCD BM plus B10.BR T cells also either were left untreated (▪, n = 8) or were administered bortezomib (•, n = 10) on day 0 immediately before TBI. Data are cumulative results from 2 experiments at each T-cell dose. Percentages of donor T-cell chimerism in the spleen (C) and overall spleen (D) and thymic (E) cellularity of mice described in panel A that survived 60 days after transplantation are shown (□, TCD BM; ▪, TCD BM/bortezomib; ▨, TCD BM/spleen cells/bortezomib). Data in bar graphs are presented as the mean ± SEM. Spleen cellularity: TCD versus TCD/bortezomib, P = .53; TCD/bortezomib versus TCD/spleen/bortezomib, P = .002. Thymus cellularity: TCD versus TCD/bortezomib, P = 0.94; TCD/bortezomib versus TCD/spleen/bortezomib, P = .02.
