Inhibiting RAR signaling in donor T cells prevents GVHD lethality. (A) Survival and weight curves of lethally irradiated B10.BR recipients of 10⁷ BM cells and 10⁷ splenocytes from B6 mice. Recipients of splenocytes from dnRARα-CD4^Cre mice (filled circles) survived significantly longer than recipients of dnRARα splenocytes (open circles; P < .001; n = 16/group). (B) Survival, weight, and clinical GVHD scores curves of lethally irradiated BALB/c recipients of 10⁷ BM cells and 5 × 10⁶ splenocytes from B6 mice. Recipients of splenocytes from dnRARα-CD4^Cre mice (filled circles) survived significantly longer than recipients of dnRARα splenocytes (open circles) (P < .001; n = 13-14/group). (C) Tissues (lung, liver, spleen, small intestine, and colon) from B10.BR recipients or BALB/c recipients were harvested on day 21 posttransplant, stained with hematoxylin and eosin, and scored for GVHD (means ± standard error). (D) FITC-dextran was orally administered to BALB/c recipients on day 21. Serum FITC-dextran levels were measured 4 hours later. Mice received wt BM cells unless otherwise indicated (P = .007). Data are combined from 2 experiments with similar results or 1 experiment each with 4 to 5 (C) or 5 to 7 (D) mice per group. (C-D) *P > .05; **P > .01; and ***P > .001.