Recipients of FasL-defective B6.gld donor T cells develop significantly less GVHD but do not die of leukemia.

All C3FeB6F1/J recipients received, on day 0, lethal irradiation (1300 cGy) followed by intravenous injection of B6 TCD-BM cells (5 × 10⁶) and 32Dp210 leukemia cells (10³). In addition, some recipients received splenic T cells (2 × 10⁶) from normal B6, B6.gld, or B6.pfp^−/− donors. (A) Recipients of B6 TCD-BM succumbed to leukemia, and hepatosplenomegaly was observed at autopsy. Hepatic tissue was preserved in formalin (10%) and embedded in paraffin, and tissue sections were stained with hematoxylin and eosin. Histopathologic examination revealed extensive periportal leukemic infiltration (large picture; original magnification, 100×), with many large anaplastic cells with pleomorphic, multilobular large nuclei and frequent mitotic figures (arrow, inset; original magnification, 1000×). Recipients of B6 TCD-BM only or B6 TCD-BM + B6.gld T cells developed less GVHD as determined by weight loss (B) and clinical GVHD score (C). The overall survival in recipients of TCD-BM + B6.gld was significantly better than in all other groups (D) (recipients of B6.gld T cells vs other recipients, P < .0001). Data from 2 combined experiments with 16 recipients per group are shown. This experiment was repeated without the inoculation of leukemia (E), and the survival of recipients of B6.gld was again significantly better than the survival of recipients of B6 T cells or B6.pfp^−/− T cells. Each group consisted of 8 animals.