Figure 2.

GITR stimulation induces paradoxical responses in CD4+ CD25− and CD8+CD25− T cells in vitro and in vivo. (A) An anti-GITR agonist Ab (DTA-1; 10 μg/ml) was added to MLRs of purified CD4+CD25− and CD8+CD25− splenic T cells as effector cells (105) with irradiated splenocytes as stimulators (2 × 105). (Wild-type stimulators) C57BL/6 effectors and BALB/c stimulators. (GITR+/− and GITR−/− stimulators) BALB/c effectors and GITR+/− or GITR−/− stimulators (C57BL/6 × 129/SvJ). −Stim, without stimulators. +Stim, with stimulators. *, P < 0.001. (B) Proliferative profile of recovered CFSE-labeled CD4+CD25− and CD8+CD25− T cells from sublethally irradiated hosts treated with 10 μg/ml DTA-1 or rat IgG control. These data are representative of three independent experiments. (top left) Percentage of alloreactive fast-proliferating donor T cells. (center) Percentage of slow proliferating donor T cells. (top right) Nondividing donor T cells.