Reduced GVHD lethality as a consequence of inhibiting IL-21/IL-21R signaling on donor T cells. Survival and weight curves of lethally irradiated B10.BR recipients of T cell–depleted BM and Teffs from B6 mice. * indicates recipients of wt BM if not otherwise indicated. Recipients of 10⁶ wt CD4⁺CD25⁻ T cells treated with irrelevant IgG (▾) or anti–IL-21Ab (▿; P = .01; A-B). Recipients of CD4⁺CD25⁻ T cells from wt (▾) and IL-21^−/− (▿) donors (P < .001; C-D). Recipients of CD25⁻ T cells from wt (▾) or IL-21^−/− (▿) donors (P < .001; E-F). Recipients of IL-2γcR^−/− BM (*) plus wt (▾) or IL-21^−/− (▿) CD25⁻ T cells (P < .001; C-D). Data from 2, 1, 4, and 1 experiments with 16, 8, 22, and 12 mice per group for panels A and B, C and D, E and F, and G and H, respectively.