Granzyme K Expressing Cytotoxic T Lymphocytes Protects Against Influenza Virus in Granzyme AB −/− Mice

Granzyme (grz) AB^−/− H2^b mice generate numerically normal cytotoxic T lymphocyte (CTL) responses to the prominent influenza A virus D^b NP₃₆₆ and D^b PA₂₂₄ epitopes and terminate the infectious process in the pneumonic lung with the same kinetics as the WT controls. Though grz B protein expression is fully compromised, there is only a partial effect on the level of CTL activity measured in a classical, short-term ⁵¹Cr release assay. Single-cell polymerase chain reaction (PCR) analysis of both highly activated effector and “resting” memory CD8⁺ T cells from influenza A virus–infected grzAB^−/− mice showed a high prevalence of grzK mRNA⁺ expression in tetramer (tet)⁺ CTLs as was found in WT mice. However, a marked reduction in cytotoxicity present in the primary splenic CTLs of grzAB^−/− mice correlated with decreased grzK expression, as measured by real-time PCR. This suggests that grzK plays an important role in CD8⁺ T-cell cytotoxicity both in the presence and absence of grzA and B.