In vitro-differentiated TH17 cells induce lethal acute GVHD. Whole splenic T cells (5 × 10⁶; n = 7) or CD4⁺/CD25⁻ sorted cells (5 × 10⁶; n = 12) or TH17 cells (n = 8; differentiated as in Figure 1) were transferred with T cell–depleted bone marrow cells into lethally irradiated B6D2 recipients. Animals were monitored for survival (A) and signs of GVHD (B). *P values at all of the statistically significant time points were at most .04. Whole splenic T cells (3 × 10⁶; n = 11) or TH17s (3 × 10⁶; n = 13) were transferred with T-cell-depleted bone marrow cells into lethally irradiated B6D2 recipients. Animals were monitored for (C) survival and (D) signs of GVHD. (*P < .04; **P values remained significant from day 14 on.) TH17 cells were transferred with whole T cells in different doses and T cell–depleted bone marrow cells into lethally irradiated B6D2 recipients (2 × 10⁶ whole T cells plus 10⁶ TH17 cells, n = 13; 10⁶ whole T cells plus 2 × 10⁶ TH17 cells, n = 9). Animals were monitored for (E) survival and (F) signs of GVHD. (*P < .04; **P values remained significant from day 35 on.) For each experiment animals receiving bone marrow only (n = 4) served as controls for GVHD. (G) Comparison of pathologic skin lesions in recipients of 5 × 10⁶ whole splenic T cells (left animal) versus recipients of TH17 cells (right animal) at day 25 after transplantation. (H) Pathologic skin lesions in recipients of TH17 cells at day 38 after transplantation.