FIGURE 3. Restoration of function in 'helpless' exhausted CD8 T cells.

Mice were depleted of CD4 T cells and then infected with LCMV clone 13. After at least 40 days, chronically infected mice were treated with anti-PD-L1 for two weeks. Frequency and total number of tetramer-positive CD8 T cells in the spleen (a, b) or indicated tissues (c) (P < 0.0001 for GP33 and GP276). d, BrdU incorporation and Ki67 expression. n > 7 mice per group. e, Percentage of D^bGP276–286 tetramer-positive cells capable of producing IFN- (P < 0.0001). f, Direct ex vivo⁵¹Cr-release activity using target cells coated with GP33–41, GP276–286 and GP118–125 peptides (effector:target ratio of 100:1). g, To measure degranulation by LCMV-specific CD8 T cells, splenocytes were stimulated with peptide in the presence of anti-CD107a/b antibodies and then co-stained for IFN-. h, Viral titres in the indicated tissues. n > 10 mice. (spleen P = 0.008, liver P < 0.0001, lung P = 0.0002, serum P = 0.03).