FIG. 8.

Virus-specific CD8⁺ T cells in nonlymphoid tissues experience functional exhaustion with a hierarchical loss of IL-2, TNF-α, and IFN-γ during chronic infections. C57BL/6 mice were infected with 10² (A) or with 2 × 10⁶ (B) PFU of LCMV-Docile, and lymphocytes were isolated from the spleen and liver at the indicated times. The total numbers of virus- or GP133-41 or NP396-404 epitope-specific CD8⁺ T cells producing IFN-γ (•), TNF-α (▴), or IL-2 (▾) after short-term culturing with virus-infected DC2.4 cells or peptide, respectively, are shown. For a comparison, the numbers of total (sum of GP133-41 and NP396-404) (left panels), GP133-41 (middle panels), or NP396-404 (right panels) peptide-specific CD8⁺ T cells were determined by staining with H-2D^b tetramers (▪). Data shown are means ± SEM of log₁₀ virus-specific T cells per tissue for 5 to 10 mice.