STAT6 deficiency allows only for partial protection by AT while L-mevalonate reverses the protective statin effect. C57BL/6 mice (H-2^b, Th-1.1) were given 5 × 10⁶ TCD-BM cells and 2 × 10⁶ CD4⁺/CD8⁺ (4:1) T cells (both H-2^d, Thy-1.2) after lethal irradiation with 800 cGy. Donor animals were fed with either PBS or AT for 10 days prior to transplantation. (A) Survival of mice receiving TCD-BM (▵, n = 15) with T cells from PBS-treated donors (□, n = 15), atorvastatin-treated (AT, 10 mg/kg) wt donors (■, n = 15), and STAT6-deficient donors treated with PBS (●, n = 15) or AT (○, n = 15). Percentage survival of Balb/c recipients is significantly higher when T cells are derived from wt donors as compared with STAT6-deficient donors when both are treated with AT (■ vs ○, P = .02). Data from 2 independent experiments are combined. (B) Survival of mice receiving TCD-BM (▵, n = 15) with T cells from PBS-treated donors (□, n = 15), atorvastatin-treated (AT, 10 mg/kg) donors (■, n = 15), AT with L-mevalonate pretreatment (○, n = 15), and PBS with L-mevalonate (●, n = 15). Percentage survival of Balb/c recipients is significantly higher when T cells are derived from AT as compared with AT with L-mevalonate–treated donors (■ vs ○, P = .004). Data from 2 independent experiments are combined. (C) In vivo expansion of CFSE-labeled Balb/c (H-2K^d, Thy-1.2⁺) CD4 T cells in C57BL/6 recipients (H-2K^d Thy-1.1⁺) on day 3 after BMT is depicted. Percentages of T cells having undergone cell division are indicated in the left upper corner of each histogram. Proliferation of T cells in the group pretreated with AT is significantly reduced as compared with PBS, STAT6^−/− with AT, and AT with L-mevalonate (P < .05). (D) At 10 days after transplantation, mice from the indicated group were killed and sections of small bowel, large bowel, and liver were stained with H&E. Slides were analyzed by a pathologist blinded to the treatment groups (N.K.) for evidence of pathologic damage. Histopathologic scoring was performed as described in “GVHD histopathology scoring” with a range from 0 (absence of GVHD signs) to 4 (maximal GVHD damage). Data are pooled from 3 experiments, representing 6 animals per group. (E) Histopathologic evaluation of representative liver samples collected 10 days after transplantation is shown for the PBS group (i) and the groups where donor T cells are derived from AT-treated wt (ii) or STAT6^−/− (iii) donors. Maximal liver tissue damage and strong lymphocytic infiltration surrounding the bile duct region as indicated by the solid arrow (i), minimal tissue damage (ii), intermediate liver damage, and low degree of lymphocytic infiltration surrounding the bile duct (iii) (dashed arrow). Magnification is ×400.