Figure 4
Figure 4. Sunitinib treatment decreases thymic progenitors and enhances thymic and peripheral lymphoid donor chimerism after BMT. (A-B) WT mice received sunitinib or vehicle as described in Figure 1A, and thymi were analyzed on day 4. (A) Representative flow cytometry plot showing diminished frequencies of DN1 thymocytes and thymic ETPs in sunitinib- (bottom panel) versus vehicle- (top panel) treated mice. (B) Sunitinib did not significantly decrease the percentage of CD44+CD25− DN1 thymocytes (represented by total of stacked bar graphs), but it did induce a selective, significant decline of the KIT+ ETP (white stacked bar graph) within the DN1 population. Data represent pooled results from 4 independent experiments; n = 20 mice/group. (C-F) Rag1−/− recipients received sunitinib or vehicle for 4 days, followed by transfer of 5 × 106 TCD congenic BM cells from WT C57Bl/6 mice on days 0 and 1. On day 28 after BMT, sunitinib recipients showed increased numbers of donor-derived Lin− thymocytes (C), increased thymic weight (D), increased total thymocyte numbers (E), increased numbers of donor-derived splenic CD3+ (F), and splenic B cells (CD3−B220+MHCII; G) compared with vehicle controls. Radiation therapy composed Rag1−/− recipients conditioned with 1000 cGY before BMT as controls. Data represent pooled results from 3 independent experiments. In scatterplots, each shape represents a mouse from day 28 of panels C and F. Day 14, n = 4 or 5 mice/group; day 28, n = 8 to 13 mice/group; day 84, n = 4 to 15 mice/group. Data represent pooled results from 2 independent experiments. Experiments were repeated 2 to 5 times with similar results. *P < .05. **P < .005. ***P < .001.

Sunitinib treatment decreases thymic progenitors and enhances thymic and peripheral lymphoid donor chimerism after BMT. (A-B) WT mice received sunitinib or vehicle as described in Figure 1A, and thymi were analyzed on day 4. (A) Representative flow cytometry plot showing diminished frequencies of DN1 thymocytes and thymic ETPs in sunitinib- (bottom panel) versus vehicle- (top panel) treated mice. (B) Sunitinib did not significantly decrease the percentage of CD44+CD25 DN1 thymocytes (represented by total of stacked bar graphs), but it did induce a selective, significant decline of the KIT+ ETP (white stacked bar graph) within the DN1 population. Data represent pooled results from 4 independent experiments; n = 20 mice/group. (C-F) Rag1−/− recipients received sunitinib or vehicle for 4 days, followed by transfer of 5 × 106 TCD congenic BM cells from WT C57Bl/6 mice on days 0 and 1. On day 28 after BMT, sunitinib recipients showed increased numbers of donor-derived Lin thymocytes (C), increased thymic weight (D), increased total thymocyte numbers (E), increased numbers of donor-derived splenic CD3+ (F), and splenic B cells (CD3B220+MHCII; G) compared with vehicle controls. Radiation therapy composed Rag1−/− recipients conditioned with 1000 cGY before BMT as controls. Data represent pooled results from 3 independent experiments. In scatterplots, each shape represents a mouse from day 28 of panels C and F. Day 14, n = 4 or 5 mice/group; day 28, n = 8 to 13 mice/group; day 84, n = 4 to 15 mice/group. Data represent pooled results from 2 independent experiments. Experiments were repeated 2 to 5 times with similar results. *P < .05. **P < .005. ***P < .001.

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