Figure 7
Figure 7. Recipients of RAR-α–deficient T cells are protected from lethal GVHD yet are able to mount a GVL response. Lethally irradiated Balb/c mice were transplanted with BM cells (5 × 106) from either RAR-α─/─ (□) or wild type (WT) littermate controls (○) or BM and spleen cells (adjusted to yield a T-cell dose of 0.7−1.0 × 106 T cells) from either RAR-α─/─ (▪) or WT littermate controls (●). (A) Overall survival. Data are cumulative results from 3 independent experiments (n = 3 for BM control groups, n = 14 for each BM + T-cell group). (B) Lethally irradiated Balb/c mice were transplanted with BM (5 × 106) and spleen cells (adjusted to yield a T-cell dose of 2.1 × 106) from either RAR-α─/─ (n = 9) or WT littermate controls (n = 5). Mice were killed at days 10 to 12 after BMT and pathological damage in the liver, lung, and colon was examined. Data are derived from 2 independent experiments and are presented as the mean (± standard error of the mean [SEM]). Representative photomicrographs of the colon from mice transplanted with WT vs RAR-α─/─ marrow grafts are shown. Colon from recipients of WT grafts show loss of mucin and destruction of crypt architecture, while animals reconstituted with grafts from RAR-α─/─ mice have normal-appearing crypts. Statistics: *P ≤ .05, ***P ≤ .001. (C,D) The absolute number of donor-derived CD4+ (C) and CD8+ cells (D) in the liver, spleen, lung, and colon is shown for each group. Data are derived from 2 independent experiments and are presented as the mean (± SEM). (E) Lethally irradiated Balb/c mice were administered 0.6 × 106 A20 cells transfected with firefly luciferase (A20-luc) and then transplanted with WT BM alone (n = 5), WT BM plus spleen cells (adjusted to yield a dose of 1.2 × 106 T cells; n = 5), or RAR-α─/─ BM plus spleen cells (adjusted to yield an equivalent T cell dose; n = 5). Overall survival and whole body distribution of A20-luc cells using in vivo BLI is depicted.

Recipients of RAR-α–deficient T cells are protected from lethal GVHD yet are able to mount a GVL response. Lethally irradiated Balb/c mice were transplanted with BM cells (5 × 106) from either RAR-α─/─ (□) or wild type (WT) littermate controls (○) or BM and spleen cells (adjusted to yield a T-cell dose of 0.7−1.0 × 106 T cells) from either RAR-α─/─ (▪) or WT littermate controls (●). (A) Overall survival. Data are cumulative results from 3 independent experiments (n = 3 for BM control groups, n = 14 for each BM + T-cell group). (B) Lethally irradiated Balb/c mice were transplanted with BM (5 × 106) and spleen cells (adjusted to yield a T-cell dose of 2.1 × 106) from either RAR-α─/─ (n = 9) or WT littermate controls (n = 5). Mice were killed at days 10 to 12 after BMT and pathological damage in the liver, lung, and colon was examined. Data are derived from 2 independent experiments and are presented as the mean (± standard error of the mean [SEM]). Representative photomicrographs of the colon from mice transplanted with WT vs RAR-α─/─ marrow grafts are shown. Colon from recipients of WT grafts show loss of mucin and destruction of crypt architecture, while animals reconstituted with grafts from RAR-α─/─ mice have normal-appearing crypts. Statistics: *P ≤ .05, ***P ≤ .001. (C,D) The absolute number of donor-derived CD4+ (C) and CD8+ cells (D) in the liver, spleen, lung, and colon is shown for each group. Data are derived from 2 independent experiments and are presented as the mean (± SEM). (E) Lethally irradiated Balb/c mice were administered 0.6 × 106 A20 cells transfected with firefly luciferase (A20-luc) and then transplanted with WT BM alone (n = 5), WT BM plus spleen cells (adjusted to yield a dose of 1.2 × 106 T cells; n = 5), or RAR-α─/─ BM plus spleen cells (adjusted to yield an equivalent T cell dose; n = 5). Overall survival and whole body distribution of A20-luc cells using in vivo BLI is depicted.

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