Cutaneous GVHD is CD4-independent but requires signaling through the donor IL-17 and IL-21 receptor. (A) Clinical scores 6 weeks after transplantation of lethally irradiated B6 recipients (n = 10 per group) of G-CSF–mobilized BALB/c.WT grafts containing both CD4 and CD8 T cells or equivalent numbers of CD8 T cells only. A non-GVHD control group received TCD G-CSF–mobilized splenocytes only (n = 6). ^ΦP < .001, CD4 plus CD8 vs CD8. (B) Semiquantitative histopathology of skin 6 weeks after BMT (n = 9 or 10 per GVHD group and n = 6 in TCD group). **P < .01, *P < .05, CD4 plus CD8 T and CD8 T vs TCD, respectively. (C) Representative histopathology at week 6 after BMT (original magnification ×200). (D) Semiquantitative skin histopathology 5 weeks after transplantation in lethally irradiated B6D2F1 recipients (n = 5-9 per group) transplanted with G-CSF–mobilized B6.WT, B6.IL-21R^−/− or B6.IL-17R^−/− splenocytes. A non-GVHD control group received B6.WT T-cell-depleted G-CSF–mobilized splenocytes only (n = 4). *P < .05, WT vs IL-21R^−/− and IL-17R^−/−. (E) Representative histopathology at week 7 after BMT (original magnification ×100).