CD73 deficiency causes enhanced GVHD mortality. All BMTs were performed on lethally irradiated mice as described in “BMT model and induction of GVHD,” and survival was monitored for the indicated times. (A) Cd73^+/+ (n = 12) and Cd73^−/− (n = 13) BALB/c mice were transplanted with 5 × 10⁶ BM cells with or without 10 × 10⁶ splenocytes from Cd73^+/+ or Cd73^−/− C57BL/6 mice, respectively (P < .0001). (B) Cd73^+/+ and Cd73^−/− C57BL/6 mice were transplanted with 5 × 10⁶ BM cells with or without 15 × 10⁶ splenocytes from Cd73^+/+ or Cd73^−/− BALB/c mice, respectively (n = 10/group). P < .0001. (A-B) Results are representative of 3 independent experiments. (C) Cd73^+/+ BALB/c mice were transplanted with 5 × 10⁶ BM cells with or without 3 × 10⁵ CD4⁺/CD8⁺ splenic T cells from Cd73^+/+ or Cd73^−/− C57BL/6 mice (n = 22/group; data pooled from 4 experiments). P = .0045. (D) Cd73^+/+ and Cd73^−/− C57BL/6 mice were transplanted with 5 × 10⁶ BM cells and 2 × 10⁵ CD4⁺/CD8⁺ splenic T cells from a Cd73^+/+ BALB/c donor (n = 11/group; data pooled from 2 experiments). P = .0019. (E) Cd73^+/+ (n = 11) and Cd73^−/− (n = 13) C57BL/6 mice were transplanted with 5 × 10⁶ BM cells and 1 × 10⁶ CD4⁺/CD8⁺ splenic T cells from a Cd73^+/+ FVB/N donor (data pooled from 3 experiments). P = .0052. (F) Cd73^+/+ C57BL/6 mice were transplanted with 5 × 10⁶ BM cells and 2 × 10⁵ CD4⁺/CD8⁺ splenic T cells from Cd73^+/+ BALB/c mice. One group (n = 10) was treated with the CD73 inhibitor APCP as described in “In vivo inhibition of CD73 and antagonism of ARs”; the other group (n = 15) received PBS as vehicle (data pooled from 3 experiments). P = .0022. (G) Cd73^+/+ and Cd73^−/− C57BL/6 mice were transplanted with 5 × 10⁶ BM cells and 1 × 10⁶ CD4⁺/CD8⁺ splenocytes from a Cd73^+/+ FVB/N donor. Ten days later, mice were killed and paraffin sections of small intestine, large intestine, and liver were stained with hematoxylin and eosin. Histopathologic scoring was performed as described in “Histopathdology scoring of acute GVHD.” Left panel: Pooled GVHD histopathology score (mean ± SEM). *P = .0058 for liver. P = .0009 for small intestine. P = .003 for colon. n = 8-10 mice/group (data pooled from 3 independent experiments). Right panel: Representative colon sections from Cd73^+/+ and Cd73^−/− recipients. Evaluation of the stained tissue sections was performed on an Axio Imager A2 microscope (Zeiss) at 400× magnification and 0.60 numerical aperture. Photos were obtained using a digital camera (Horn Imaging, model MC-MD1/3, HD capture software). Arrows indicate crypt abscesses.