Type I-IFN signaling differentially regulates CD4⁺ and CD8⁺ T-cell GVHD in a minor histocompatibility antigen-mismatched model of BM transplantation. Survival of lethally irradiated B6.WT or B6.IFNAR1^−/− mice transplanted with 10⁷ BM and either (A) 3 × 10⁶ CD4⁺ T cells only (*P < .05, B6.IFNAR1^−/− vs B6.WT recipients; n = 13 in BM + T, n = 6 in TCD controls), (B) 2 × 10⁶ CD8⁺ T cells only (*P < .05, B6.IFNAR1^−/− vs B6.WT recipients, n = 16 in BM + T, n = 4 in syngenic controls), or (C) CD3⁺ T cells containing 2 × 10⁶ CD8⁺ T cells (^#P < .005, B6.IFNAR1^−/− vs B6.WT recipients, n = 16 in BM + T, n = 8 in TCD controls) from immunized C3HSW mice. (D) Clinical scores of lethally irradiated B6.WT or B6.IFNAR1^−/− mice who underwent transplantation with 5 × 10⁶ BM and 5 × 10⁶ CD3⁺ T cells from bm1 donors (*P < .05, **P < .01, ^#P < .005, B6.IFNAR1^−/− vs B6.WT recipients, n = 16 in BM + T, n = 8 in TCD controls, data combined from 2 experiments). (E) At day 12 after transplantation with CD3⁺ T cells in the bm1 → B6 system, CD8⁺ T cells were sort purified and used as effectors in chromium release assays against host type EL4 or donor bm1 blasts as targets. (F) At day 21 after transplantation with CD3⁺ T cells in the C3H.SW → B6 system, CD8⁺ T cells were enumerated (data combined from 2 experiments, mean ± SEM; n = 8 per group), stained for Granzyme B (mean ± SEM; n = 4 per group), or sort purified then used as effectors in chromium release assays against host type EL4 or donor C3H.SW blasts as targets (data combined from 2 experiments). (G) In vivo CTL function against B6.CD45.1⁺ and CFSE-labeled B6.IFNAR1^−/− (CD45.2⁺) host targets at day 12 after transplantation in the C3H.SW → B6 system (GVHD recipients received BM and CD3⁺ T cells, and non-GVHD recipients received T cell–depleted BM only). The ratio of remaining B6.IFNAR1^−/− to B6.CD45.1⁺ targets in spleen is shown with representative plots (^#P = .005, no GVHD vs GVHD; data combined from 2 experiments, mean ± SEM; n = 7-10 per group). (H) IFNAR1 expression on the P815, P210, A20, EL4, and 5GTM1 tumor cell lines.