CD122 expression on CD8+ T cells identifies severely exhausted cells. C57BL/6 (B6) mice were infected with LCMV Cl-13; analyses were performed in spleens on day 21 p.i. unless otherwise indicated. (A) Cell-surface expression of CD132 (left y axis; filled squares represent Δ MFI) and viral titers (right y axis; dashed gray line) at the indicated time points. (B) Intracellular expression of p-STAT5 in activated (CD11a+) CD8+ T cells following stimulation with the indicated cytokines from animals infected with LCMV Arm (acute infection; red bars) or LCMV Cl-13 (chronic infection; black bars) at day 30 p.i.; Unstim, level in unstimulated control. (C) Gating strategy for CD122hi H-2Dbgp33+CD8+ T cells (upper gate) and CD122lo H-2Dbgp33+CD8+ T cells (lower gate). Gates are set above and below the center of the population. CD122int/lo cells include cells negative for CD122. Values indicate the frequency in each gate. (D) Frequency of CD122lo (black bars) and CD122hi (white bars) H-2Dbgp33+CD8+ T cells producing IFNγ, TNFα, or both IFNγ and TNFα simultaneously. *P < 0.05; **P < 0.005; ***P < 0.0005; NS P ≥ 0.05; two-tailed unpaired Student’s t test. Data are pooled from two (A) or three (D) independent experiments with four to eight mice per group or are representative of three (C) or four (B) independent experiments with similar results (two to three mice per group in each). Error bars in A, B, and D indicate mean ± SEM.