Figure 4. The ability of hyperactive mTORC1 signaling to promote effector function is cell intrinsic.

(A) OT-I⁺CD90.1⁺CD8⁺ T cells from WT, T-Rheb^–/–, and T-Tsc2^–/– mice were adoptively transferred into WT CD90.2⁺ recipient mice infected with vaccinia-OVA. Six days after infection, splenocytes were harvested. The percentage of splenic CD8⁺ CD90.1⁺ T cells, KLRG1 expression of CD8⁺CD90.1⁺ cells, and IFN-γ and TNF-α production after SIINFEKL peptide stimulation are shown, with statistics to the right (n = 10). For the box-and-whiskers plots, the whiskers represent the minimum and maximum values, the box boundaries represent the 25th and 75th percentiles, and the middle line is the median value. (B) WT and T-Tsc2^–/– mice received s.q. EL4 thymoma cells expressing luciferase. Tumor burden was assessed by detection of luminescence (n = 16). (C–E) In vitro–activated T-Rheb^–/– and T-Tsc2^–/– and littermate control OT-I⁺CD8⁺ T cells were injected into WT recipients that had received B16-OVA cells 6 days prior (dashed line represents T cell transfer). “No transfer” indicates that mice did not receive OT-I⁺ cells. (C) Tumor volume was assessed every 2 to 3 days. Each symbol represents an average per genotype (n = 15). (D) Tumor volume shown at day 24 after tumor inoculation. Each dot represents a mouse. Data are derived from C. (E) Survival was assessed. Mice that received T-Tsc2^–/– cells had enhanced survival compared with all other treatments, as determined by multiple comparisons Mantel-Cox tests. Statistics in A and D were determined by ANOVA and for B and C were determined by repeated-measures analysis. Data are representative of at least 3 independent experiments. *P < 0.05, **P < 0.01, ***P < 0.001