Figure 3
Figure 3. AT and FLU recipient treatment reduced expression of costimulatory molecules and MHC class II on antigen-presenting cells in liver and lymphoid organs. (A) Representative flow cytometric analysis of the cell surface expression of CD80, CD86, CD40, and MHC class II on CD11c+ APCs isolated from Balb/c recipients after 10 days of feeding with phosphate-buffered saline (PBS, heavy black line), atorvastatin (AT, red line), or fluvastatin (FLU, blue line) prior to transplantation (day 0). The thin black line represents the isotype control. (B) Recipient-type APCs were isolated on day 2 after transplantation from the indicated organs. The mean fluorescence intensity of the H-2KdCD11c gated population is quantified for the indicated surface molecules (PBS vs AT, *P < .05). (C) IL-4 and IL-10 expression within the CD4+ T-cell population derived from the spleen prior to transplantation is shown. AT and FLU pretreatment as described in panel A increases the frequency of CD4+IL-4+IL-10+ T cells as well as CD4+IL-4−IL-10+ Tr-1 regulatory cells. One representative FACS analysis of 3 independent experiments is shown. (D) Balb/c mice were given 5 × 106 TCD-BM cells and 1.2 × 106 CD4+/CD8+ (4:1) T cells (both H-2q) after lethal irradiation with 800 cGy. Recipient animals were fed with either PBS or the indicated statin by oral gavage for 10 days prior to transplantation. Survival of mice receiving TCD-BM (●, n = 10) plus T cells, and being pretreated with PBS (▵, n = 10), fluvastatin (○, n = 10), or atorvastatin (■, n = 10). Survival of Balb/c recipients is significantly higher when recipients are treated with FLU or AT as compared with PBS (○ vs ▵, P = .004; ■ vs ▵, P = .006). (E) Expansion of luciferase-labeled (luc+) T cells was quantified in emitted photons over total body area at serial time points after BMT in mice receiving TCD-BM (●, n = 10) and being pretreated with PBS (▵, n = 10), fluvastatin (FLU, ○, n = 10), or atorvastatin (AT, ■, n = 10). Signal intensity is significantly higher in animals pretreated with PBS only as compared with FLU- and AT-treated animals (▵ vs ○, P = .003; ▵ vs ■, P < .003). Data from 2 independent experiments are combined.

AT and FLU recipient treatment reduced expression of costimulatory molecules and MHC class II on antigen-presenting cells in liver and lymphoid organs. (A) Representative flow cytometric analysis of the cell surface expression of CD80, CD86, CD40, and MHC class II on CD11c+ APCs isolated from Balb/c recipients after 10 days of feeding with phosphate-buffered saline (PBS, heavy black line), atorvastatin (AT, red line), or fluvastatin (FLU, blue line) prior to transplantation (day 0). The thin black line represents the isotype control. (B) Recipient-type APCs were isolated on day 2 after transplantation from the indicated organs. The mean fluorescence intensity of the H-2KdCD11c gated population is quantified for the indicated surface molecules (PBS vs AT, *P < .05). (C) IL-4 and IL-10 expression within the CD4+ T-cell population derived from the spleen prior to transplantation is shown. AT and FLU pretreatment as described in panel A increases the frequency of CD4+IL-4+IL-10+ T cells as well as CD4+IL-4IL-10+ Tr-1 regulatory cells. One representative FACS analysis of 3 independent experiments is shown. (D) Balb/c mice were given 5 × 106 TCD-BM cells and 1.2 × 106 CD4+/CD8+ (4:1) T cells (both H-2q) after lethal irradiation with 800 cGy. Recipient animals were fed with either PBS or the indicated statin by oral gavage for 10 days prior to transplantation. Survival of mice receiving TCD-BM (●, n = 10) plus T cells, and being pretreated with PBS (▵, n = 10), fluvastatin (○, n = 10), or atorvastatin (■, n = 10). Survival of Balb/c recipients is significantly higher when recipients are treated with FLU or AT as compared with PBS (○ vs ▵, P = .004; ■ vs ▵, P = .006). (E) Expansion of luciferase-labeled (luc+) T cells was quantified in emitted photons over total body area at serial time points after BMT in mice receiving TCD-BM (●, n = 10) and being pretreated with PBS (▵, n = 10), fluvastatin (FLU, ○, n = 10), or atorvastatin (AT, ■, n = 10). Signal intensity is significantly higher in animals pretreated with PBS only as compared with FLU- and AT-treated animals (▵ vs ○, P = .003; ▵ vs ■, P < .003). Data from 2 independent experiments are combined.

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