Fig. 6.
FasL pathway is important for GVHD activity by donor CD4+ and CD8+ T cells but is not required for GVL activity by donor CD8+ T cells.
(A) All C3FeB6F1/J recipients underwent transplantation, as illustrated in Figure 1, with 106 purified donor CD4+splenic T cells (see “Materials and methods”) and a leukemia dose of 5000 cells/mouse. Survival is depicted as a Kaplan-Meier curve. We determined by necropsy that all recipients of B6 CD4+ T cells (■) and of B6.pfp−/− CD4+ T cells (▪) died of GVHD, whereas only one recipient of B6.gldCD4+ T cells (●) developed lethal GVHD. All other deaths in recipients of B6 BM only (○) or B6.gld CD4+T cells were from leukemia. (B) All C3FeB6F1/J recipients underwent transplantation, as illustrated in Figure 1, with 4 × 106 purified donor CD8+ splenic T cells (see “Materials and methods”) and a leukemia dose of 5000 cells/mouse. Survival is depicted as a Kaplan-Meier curve. We determined by necropsy that 5 of 6 deaths in recipients of B6 CD8+ T cells (■) were from GVHD. One of the 8 recipients of B6.pfp−/− CD8+ T cells (▪) and one recipient of B6.gld CD8+ T cells (●) died of GVHD, whereas all other deaths could be attributed to leukemia. All deaths among recipients of B6 BM only (○) were from leukemia. (C) Weight loss (as a measurement of GVHD morbidity) was determined weekly in all recipients of B6 CD8+ T cells (■) and B6.gld CD8+ T cells (●) from the BMT experiment described in panel B. Recipients of B6.gldCD8+ T cells had significantly less weight loss than recipients of B6 CD8+ T cells (P < .007). All experimental groups consisted of 8 animals, and representative results of 3 experiments with CD4+ T cells and 5 experiments with CD8+ T cells are shown.