Figure 4.
Autophagy is required during primary engraftment in the GVHD setting. (A-C) Lethally irradiated B6D2F1 mice were transplanted with WT or Atg5–/– FL cells together with CD3ε+ T cells (GVHD) or without (non-GVHD). (A) Engraftment, determined by total cell number of platelets, Hb (hemoglobin) and neutrophils in peripheral blood and total cell numbers together with CD11b+Ly6G+ (granulocytes) and CD11b+F480+ (macrophages) in BM and spleen (blood n = 14, representative of 2 repeat experiments; BM and spleen n = 4 taken from 1 representative experiment). Data are shown as mean ± SEM. Statistical significance was determined using an unpaired 2-tailed Mann-Whitney U test (∗P = .0286; ∗∗P = .0437; ∗∗∗P = .0003; and ∗∗∗∗P < .0001). (B) Survival analysis of transplant recipients given Atg5–/– or WT FL cells together with WT T cells (GVHD) or without (non-GVHD) (Atg5–/– GVHD n = 21; WT GVHD n = 16; Atg5–/– non-GVHD n = 10). (C) Flow cytometry analysis of HSC (LKE+: LinnegcKit+ESAM+) and myeloid HPC (LKEneg: LinnegcKit+ESAMneg) populations: CMP, GMP, and MEP from recipients of WT of Atg5–/– donor (GVHD) grafts at day 10 posttransplant (n = 8 representative of 2 repeat experiments). (D) In a second model: lethally irradiated B6D2F1 mice were transplanted with WT or VAVcreAtg7fl/fl BM together with WT T cells (GVHD) or without them (non-GVHD). Survival analysis of transplant recipients given WT or VAVcreAtg7fl/fl donor grafts with WT T cells or without (GVHD n = 10; non-GVHD n = 6 representative of 2 repeat experiments). (E) In a third model: lethally irradiated B6D2F1 mice were transplanted with WT or Lyz2creAtg7fl/fl BM together with WT T cells (GVHD) or without (non-GVHD). Survival and clinical scores comparing WT GVHD and Lyz2creAtg7fl/fl GVHD groups (n = 11 and 12, respectively; representative of 2 repeat experiments). Transplant data are shown as mean ± SEM. Statistical significance was determined using an unpaired 2-tailed Mann-Whitney test U test (∗∗P = .0070; ∗∗∗P = .0003). Survival curves were analyzed using a log-rank (Mantel-Cox) test (∗∗∗∗P < .0001).

Autophagy is required during primary engraftment in the GVHD setting. (A-C) Lethally irradiated B6D2F1 mice were transplanted with WT or Atg5–/– FL cells together with CD3ε+ T cells (GVHD) or without (non-GVHD). (A) Engraftment, determined by total cell number of platelets, Hb (hemoglobin) and neutrophils in peripheral blood and total cell numbers together with CD11b+Ly6G+ (granulocytes) and CD11b+F480+ (macrophages) in BM and spleen (blood n = 14, representative of 2 repeat experiments; BM and spleen n = 4 taken from 1 representative experiment). Data are shown as mean ± SEM. Statistical significance was determined using an unpaired 2-tailed Mann-Whitney U test (∗P = .0286; ∗∗P = .0437; ∗∗∗P = .0003; and ∗∗∗∗P < .0001). (B) Survival analysis of transplant recipients given Atg5–/– or WT FL cells together with WT T cells (GVHD) or without (non-GVHD) (Atg5–/– GVHD n = 21; WT GVHD n = 16; Atg5–/– non-GVHD n = 10). (C) Flow cytometry analysis of HSC (LKE+: LinnegcKit+ESAM+) and myeloid HPC (LKEneg: LinnegcKit+ESAMneg) populations: CMP, GMP, and MEP from recipients of WT of Atg5–/– donor (GVHD) grafts at day 10 posttransplant (n = 8 representative of 2 repeat experiments). (D) In a second model: lethally irradiated B6D2F1 mice were transplanted with WT or VAVcreAtg7fl/fl BM together with WT T cells (GVHD) or without them (non-GVHD). Survival analysis of transplant recipients given WT or VAVcreAtg7fl/fl donor grafts with WT T cells or without (GVHD n = 10; non-GVHD n = 6 representative of 2 repeat experiments). (E) In a third model: lethally irradiated B6D2F1 mice were transplanted with WT or Lyz2creAtg7fl/fl BM together with WT T cells (GVHD) or without (non-GVHD). Survival and clinical scores comparing WT GVHD and Lyz2creAtg7fl/fl GVHD groups (n = 11 and 12, respectively; representative of 2 repeat experiments). Transplant data are shown as mean ± SEM. Statistical significance was determined using an unpaired 2-tailed Mann-Whitney test U test (∗∗P = .0070; ∗∗∗P = .0003). Survival curves were analyzed using a log-rank (Mantel-Cox) test (∗∗∗∗P < .0001).

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