Type I-IFN signaling prevents donor T-cell proliferation and differentiation after transplantation. Lethally irradiated B6.WT or B6.IFNAR1^−/− mice were transplanted with WT.BALB/c BM and CD3⁺ T cells. (A) Sera were taken from mice at day 4 (IFN-γ) and day 7 (TNF, IL-17A, and IL-5) and cytokine levels quantified by cytometric bead array (IFN-γ, TNF, and IL-5) or ELISA (IL-17) 4 days after transplantation with BALB/c.WT BM and BALB/c.CD45.1⁺ CFSE-labeled donor cells. (B) Proliferation indices of donor CD4⁺ T cells in the spleen were calculated with ModFit Version LT3.2 software (combined data from 2 experiments; ^#P < .005; n = 8 per group). (C) Donor CD4⁺ T cells were enumerated in the spleen (combined data from 2 experiments; **P < .01; n = 8 per group), and (D) stimulated for 5 hours ex vivo and stained for IFNγ and IL-17A (plots representative of 2 experiments and displayed as mean ± SEM, n = 8 per group). (E) Survival of lethally irradiated B6.WT or B6.IFNAR1^−/− mice undergoing transplantation with 10⁷ BM and 5 × 10⁶ CD3⁺ T cells from either BALB/c.WT or BALB/c.IL-17A^−/− donors (^#P < .001, BALB/c.IL-17A^−/−→B6.IFNAR1^−/− vs both BALB/c.WT → B6.IFNAR1^−/− and BALB/c.IL-17A^−/− → B6.WT; survival curves are Kaplan-Meier estimates from 2 experiments; n = 8-16 per group).