Figure 3
Figure 3. LN, PP (aly/aly) and/or spleen-deficient mice develop GVHD. (A,B) aly/+ or aly/aly recipients were splenectomized (Spl−) or left intact 3 to 5 weeks before BMT. On day 0, recipients received 1000 cGy and 8-10 × 106 BM cells with or without 106 CD4+CD25− cells from B6bm12 donors. All CD4→aly/+ Spl− animals died by day 10 or were killed in a premorbid state for pathologic examination. Shown are combined data from 2 experiments. (A) Weight curve. †P < .01 for BM controls versus all CD4 groups for all days 6 and later; *P < .01 for CD4→aly/+ versus CD4→aly/aly or CD4→aly/aly Spl− for all days 10 and later, @P < .05 for CD4→aly/aly versus CD4→aly/aly Spl− for all days 17 and later. (B) Skin and colon histopathology. †P < .05 for BM controls versus all CD4 groups; other P values are indicated on the graphs. (C,D) On day 0, aly/+ or aly/aly recipients received 800 cGy and 107 T cell–depleted BM cells with or without 5 × 105 spleen cells from BALB/c donors. (C) Survival curve. (D) Colon histopathology at day 9 after BMT. †P < .05 for BM controls versus Spl→aly/+ or versus Spl→aly/aly. (E,F) aly/+ or aly/aly recipients were splenectomized (Spl−) or left intact 3-5 weeks before BMT. On day 0, recipients received 1000 cGy and 107 BM cells with or without 5 × 106 CD4+CD25− cells from 129/Sv donors. Shown are combined data from 2 experiments. (E) Incidence of clinical skin disease. †P < .05 for BM controls versus CD4→aly/aly or CD4→aly/aly Spl−. (F) Skin histopathology. †P < .0001 for BM controls versus CD4→aly/aly. (G) aly/aly recipients were splenectomized, allowed to rest for 3 to 5 weeks, and then transplanted with WT B6 BM (WT→aly/aly Spl−) or MHC II−/− (B6) BM (MHC II−/−→aly/aly Spl−). Eight weeks later, these mice received 2 doses of 450 cGy (separated by 3 hours) and 107 BM cells with or without 106 CD4+CD25− cells from B6bm12 donors. On day 27 after transplantation, mice were killed, and colon tissue was collected for histologic analysis. Colon histopathology; note that BM control groups are shown separately. NS indicates not significant for BM versus CD4→(MHC II−/−→aly/aly Spl−); P = .0005 for CD4→(WT→aly/aly Spl−) versus CD4→(MHC II−/−→aly/aly Spl−); P<.001 for BM versus CD4→(WT→aly/aly Spl−).

LN, PP (aly/aly) and/or spleen-deficient mice develop GVHD. (A,B) aly/+ or aly/aly recipients were splenectomized (Spl−) or left intact 3 to 5 weeks before BMT. On day 0, recipients received 1000 cGy and 8-10 × 106 BM cells with or without 106 CD4+CD25− cells from B6bm12 donors. All CD4→aly/+ Spl− animals died by day 10 or were killed in a premorbid state for pathologic examination. Shown are combined data from 2 experiments. (A) Weight curve. †P < .01 for BM controls versus all CD4 groups for all days 6 and later; *P < .01 for CD4→aly/+ versus CD4→aly/aly or CD4→aly/aly Spl− for all days 10 and later, @P < .05 for CD4→aly/aly versus CD4→aly/aly Spl− for all days 17 and later. (B) Skin and colon histopathology. †P < .05 for BM controls versus all CD4 groups; other P values are indicated on the graphs. (C,D) On day 0, aly/+ or aly/aly recipients received 800 cGy and 107 T cell–depleted BM cells with or without 5 × 105 spleen cells from BALB/c donors. (C) Survival curve. (D) Colon histopathology at day 9 after BMT. †P < .05 for BM controls versus Spl→aly/+ or versus Spl→aly/aly. (E,F) aly/+ or aly/aly recipients were splenectomized (Spl−) or left intact 3-5 weeks before BMT. On day 0, recipients received 1000 cGy and 107 BM cells with or without 5 × 106 CD4+CD25− cells from 129/Sv donors. Shown are combined data from 2 experiments. (E) Incidence of clinical skin disease. †P < .05 for BM controls versus CD4→aly/aly or CD4→aly/aly Spl−. (F) Skin histopathology. †P < .0001 for BM controls versus CD4→aly/aly. (G) aly/aly recipients were splenectomized, allowed to rest for 3 to 5 weeks, and then transplanted with WT B6 BM (WT→aly/aly Spl−) or MHC II−/− (B6) BM (MHC II−/−→aly/aly Spl−). Eight weeks later, these mice received 2 doses of 450 cGy (separated by 3 hours) and 107 BM cells with or without 106 CD4+CD25− cells from B6bm12 donors. On day 27 after transplantation, mice were killed, and colon tissue was collected for histologic analysis. Colon histopathology; note that BM control groups are shown separately. NS indicates not significant for BM versus CD4→(MHC II−/−→aly/aly Spl−); P = .0005 for CD4→(WT→aly/aly Spl−) versus CD4→(MHC II−/−→aly/aly Spl−); P<.001 for BM versus CD4→(WT→aly/aly Spl−).

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