Enhanced IFNγ generation by SOCS3^−/ΔLck T cells drives gastrointestinal tissue destruction after allogeneic SCT. SOCS3^−/ΔLck donors were treated with G-CSF, and unfractionated splenocytes containing 2 million T cells or T cell–depleted grafts were transplanted into lethally irradiated B6D2F1 recipient mice. Survival curves by Kaplan-Meier analysis. (A) Transplant recipients received isotype control mAb or anti–IL-10R thrice/week from day 7 onward. Data represent a single experiment with 10 animals/GVHD group, and 4 animals/TCD group. (B) Transplant recipients received isotype control mAb or anti–IL-17 mAb thrice/week from day 0 onward. Data are pooled from 3 similar experiments (n = 24 animals/GVHD group, n = 12 animals/TCD group). (C) Transplant recipients received T cell–replete or T cell–depleted grafts from G-CSF–treated WT or SOCS3^−/ΔLck donors, and small bowel, liver, and skin histopathology were assessed at day 7 after transplantation as described in “Histology.” (D) Images of hematoxylin and eosin–stained sections of small bowel taken day 7 after transplantation (magnification ×100). (E) Transplant recipients received isotype control mAb or anti-IFNγ on day 0, 2, and 6, and small bowel histopathology was assessed at day 7. Data are pooled from 2 similar experiments (n = 12-13 animals/GVHD group, n = 4 animals/TCD group). *P = .017 for recipients of G-CSF WT versus G-CSF SOCS3^−/ΔLck spleen. (F) Images of hematoxylin and eosin–stained sections of small bowel taken day 7 after transplantation (magnification ×100).