Fig. 7.
B6D2F1/J recipients of perforin-deficient B6.pfp−/− donor T cells display less GVL activity against P815 mastocytoma.
(A) On day 0, all B6D2F1 recipients received lethal irradiation (1300 cGy) and then B6 TCD-BM cells (5 × 106). In addition, some recipients received splenic T cells (2 × 106) from normal B6, B6.gld, or B6.pfp−/− donors. Death from GVHD is shown as a Kaplan-Meier survival curve. Recipients of B6.pfp−/− T cells had significantly fewer deaths than recipients of B6 T cells (P < .04) and more deaths than recipients of B6.gld T cells (P < .04). Combined data from 2 experiments with 16 animals per group are shown. (B, C) B6D2F1/J mice received transplants as in panel A, but all recipients received 1000 P815 mastocytoma cells in addition on day 0 after the lethal irradiation. Recipients of B6 TCD-BM succumbed to P815 mastocytoma, and hepatomegaly and liver metastases were observed at autopsy. Liver tissue was preserved in formalin (10%) and embedded in paraffin, and tissue sections were stained with hematoxylin and eosin. Histopathologic examination revealed extensive tumor infiltration with a loss of liver architecture (large picture; original magnification, 100 ×), many large round to polyhedral cells with small basophilic cytoplasmic granules, and empty vesiculated nuclei with large nucleoli and frequent mitotic figures (arrow, inset: original magnification, 1000 ×). Mortality of GVHD survivors from P815 mastocytoma is shown in panel C. Results from 3 combined experiments with 10 to 17 animals per group are shown. Recipients of B6.pfp−/− T cells had significantly more deaths than recipients of B6 T cells (P < .03) or B6.gld T cells (P = .02).