IL-2 regulates T-cell tolerance and immunity. (A–D) CD4 OT-II cells (A, B) or CD8 OT-I cells (C, D) were treated with Ova peptide or SIINFEKL peptide, respectively, in the presence of irradiated wild-type (WT) or B7−/−B7h−/− (TKO) APC with or without IL-2. After 4 days for CD4 (A) and 6–7 days for CD8 cells (C), T cells were restimulated with plate-bound α-CD3 to measure T-cell proliferation and effector cytokine (IFN-γ, IL-4, -5, -10, -13) production. Activated OT-II (B) or OT-I (D) cells were analyzed for T-bet, Eomes, Grail and HPRT mRNA expression by RT–PCR. (E) T-cell immunity or tolerance is regulated by a combinatorial costimulation signal. At resting states, when T cells encounter APC, negative costimulatory molecules PD-1, B7-H3 and B7S1 function to inactivate T cells. During infection, CD28 and ICOS ligands are upregulated on APC, which drives T cells to differentiate into effector T cells.