Figure 6.

Perforin gene correction partially restores antigen-specific CTL killing and rescues prf^−/− mice from the development of HLH-like disease after LCMV infection. Prf^−/− mice were irradiated and reconstituted with WT marrow or prf^−/− LSK transduced with PGK.PRF, PGK.PRFmut, or PRF.PRF. After 16 weeks, animals were challenged with LCMV infection. (a) On day 8 following infection, splenocytes were tested for cytotoxic function by ⁵¹Cr release assay using GP33-loaded EL4 target cells. Error bars represent SD from four mice/group. (b) Day 8 serum IFN-γ levels from animals with ≥30% chimerism of gene corrected (or WT) cells are displayed (n =10–19/group, from three experiments). (c,d) Blood hemoglobin and platelet counts were assessed in animals (with ≥30% gene-corrected chimerism) on day 15 after infection (n = 7–9/group, except PGK.PRFmut where n = 2 due to early deaths, assessed across two experiments).