Soluble LTα3 homotrimer is the important pathogenic lymphotoxin molecule in GVHD. (A) Survival by Kaplan-Meier analysis of lethally irradiated (1300 cGy) B6D2F1 mice transplanted with 5 × 10⁶ BM and 2 × 10⁶ CD3⁺ T cells from B6.WT, B6.Tnf^−/− or B6.Lta^−/− donors. Data are combined from 2 separate experiments (n = 16, BM + T groups; n = 6, TCD control group. P = .866, Tnf^−/− vs Lta^−/−; P < .009, Tnf^−/− and Lta^−/− vs WT). (B) Survival by Kaplan-Meier analysis of lethally irradiated B6D2F1 recipient mice that received BM + T grafts from B6.Lta^−/−, B6.Ltb^−/− or B6.WT donors. Data shown are combined from 2 separate experiments (n = 18, BM + T groups; n = 10, TCD control group, where TCD marrow was derived from B6 donors that were either B6.WT, B6.Lta^−/− or B6.Ltb^−/−). P = .018, Lta^−/− vs WT; P < .0001 Ltb^−/− vs WT. (C) Survival by Kaplan-Meier analysis of lethally irradiated BALB/c recipient mice transplanted with 5 × 10⁶ BM and 0.5 × 10⁶ CD3⁺ T cells from B6.Ltb^−/−, B6.Lta^−/− or B6.WT donors. Data shown are combined from 2 separate experiments (n = 12 in BM + T groups; n = 7 in TCD control group where the TCD donor was B6.Ltb^−/−. P = .0011 Lta^−/− vs WT; P = .212, Ltb^−/− vs WT). (D) Survival by Kaplan-Meier analysis of BALB/c recipients of Lta^−/− or WT grafts in which the T-cell dose was either 0.25 × 10⁶ CD3⁺ per graft, or 10⁶ CD3⁺ per graft. For 0.25 × 10⁶ T cells: n = 10 per BM + T group; P = .0357 Lta^−/− vs WT. For 10⁶ T cells: n = 20 per BM + T group; P = .1657 Lta^−/− vs WT. (E) Tissues from BALB/c recipient mice transplanted with 5 × 10⁶ BM and 0.5 × 10⁶ CD3⁺ T cells from B6.Lta^−/− (n = 7), B6.WT donors (n = 8), or B6.WT TCD controls (n = 4) were taken 21 days after transplantation. Sections were prepared and scored for histopathology, including apoptosis, as described in “Histologic analysis.” For colon: P = .0016 Lta^−/− vs WT; skin: P = .0088 Lta^−/− vs WT. Representative photomicrographs (×250) from colon and skin 21 days after BMT. (F) Collated apoptosis scores from colon and skin, as described in “Histologic analysis,” P = .023, Lta^−/− vs WT. Photomicrographs (×400) of TUNEL staining on representative colon, as described in “Histologic analysis.” (G) Survival by Kaplan-Meier analysis of lethally irradiated BALB/c recipient mice transplanted with 5 × 10⁶ BM and 0.5 × 10⁶ CD3⁺ T cells from B6.Tnf^−/−, B6.Lta^−/−, B6.Tnf/Lta^−/−, or B6.WT donors. Data shown are combined from 2 separate experiments (n = 14 in BM + T groups; n = 10 in TCD control group; P ≤ .0007 for Tnf^−/−, Lta^−/− and Tnf/Lta^−/− BM + T groups vs WT).