Figure 7
Figure 7. GVL effector function of cytolytic T cells is preserved in the presence of atorvastatin treatment of donor and recipient. Tumor growth and GVL effect are visualized by bioluminescence imaging (A), recipient survival (B), emitted photons over time (C), and FACS analysis (D). All Balb/c recipients (H-2Kd) were given 105 A20 leukemia cells (H-2Kd) on day 0 and BMT was performed as described in “Tumor models.” (A) Representative animals of each group display similar luc+A20 tumor cell localization on day 4 (top row) after BMT. Tumor elimination in animals receiving T cells on days 8 (middle row) and 16 (bottom row). Mice underwent transplantation with TCD-BM after PBS (first column) or AT (second column) treatment, TCD-BM plus T cells exposed to PBS (third column) or AT (fourth column). Tumor infiltration is found in the following locations: ST, sternum; HU, humerus; FE, femur; SPL, spleen. (B) Survival of BALB/c mice receiving TCD-BM alone (●, n = 10), TCD-BM plus A20 leukemia cells after pretreatment of donor and recipient with PBS (▵, n = 10) or AT (□, n = 10), TCD-BM plus A20 leukemia cells plus T cells after pretreatment of donor and recipient with PBS (*, n = 10) or AT (○, n = 10). Survival: ○ versus *, P < .001. Data from 2 independent experiments are combined. (C) Expansion of luc+A20 tumor cell as measured in photons over total body area (photons/second/mouse). Animals rejecting the A20 leukemia cells demonstrate a durable signal loss as depicted until day 112 after BMT. Data from 2 independent experiments are combined. (D) Bone marrow samples with yfp+ A20 cells of recipients on days 7 and 15 after transplantation with TCD-BM plus A20 leukemia cells after pretreatment of donor and recipient with PBS or AT, TCD-BM plus A20 leukemia cells plus T cells after pretreatment of donor and recipient with PBS or AT as indicated for the respective column. (E) In vitro cytolytic effector function of CD8+ T cells (FVB/N) derived from animals treated with PBS or AT. Target cells were A20 or Yac1 tumor cells and chromium release assay was performed as described in “51Cr release cytotoxicity assay.”

GVL effector function of cytolytic T cells is preserved in the presence of atorvastatin treatment of donor and recipient. Tumor growth and GVL effect are visualized by bioluminescence imaging (A), recipient survival (B), emitted photons over time (C), and FACS analysis (D). All Balb/c recipients (H-2Kd) were given 105 A20 leukemia cells (H-2Kd) on day 0 and BMT was performed as described in “Tumor models.” (A) Representative animals of each group display similar luc+A20 tumor cell localization on day 4 (top row) after BMT. Tumor elimination in animals receiving T cells on days 8 (middle row) and 16 (bottom row). Mice underwent transplantation with TCD-BM after PBS (first column) or AT (second column) treatment, TCD-BM plus T cells exposed to PBS (third column) or AT (fourth column). Tumor infiltration is found in the following locations: ST, sternum; HU, humerus; FE, femur; SPL, spleen. (B) Survival of BALB/c mice receiving TCD-BM alone (●, n = 10), TCD-BM plus A20 leukemia cells after pretreatment of donor and recipient with PBS (▵, n = 10) or AT (□, n = 10), TCD-BM plus A20 leukemia cells plus T cells after pretreatment of donor and recipient with PBS (*, n = 10) or AT (○, n = 10). Survival: ○ versus *, P < .001. Data from 2 independent experiments are combined. (C) Expansion of luc+A20 tumor cell as measured in photons over total body area (photons/second/mouse). Animals rejecting the A20 leukemia cells demonstrate a durable signal loss as depicted until day 112 after BMT. Data from 2 independent experiments are combined. (D) Bone marrow samples with yfp+ A20 cells of recipients on days 7 and 15 after transplantation with TCD-BM plus A20 leukemia cells after pretreatment of donor and recipient with PBS or AT, TCD-BM plus A20 leukemia cells plus T cells after pretreatment of donor and recipient with PBS or AT as indicated for the respective column. (E) In vitro cytolytic effector function of CD8+ T cells (FVB/N) derived from animals treated with PBS or AT. Target cells were A20 or Yac1 tumor cells and chromium release assay was performed as described in “51Cr release cytotoxicity assay.”

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