Perforin-deficient CD8⁺ T cells: In vivo priming and antigen-specific immunity against Listeria monocytogenes

CD8⁺ T cells require perforin to mediate immunity against some, but not all, intracellular pathogens. Previous studies with H-2^b MHC perforin gene knockout (PO) mice revealed both perforin-dependent and perforin-independent pathways of CD8⁺ T cell-mediated immunity to Listeria monocytogenes (LM). In this study, we address two previously unresolved issues regarding the requirement for perforin in antilisterial immunity: 1) Is CD8⁺ T cell- mediated, perforin-independent immunity specific for a single Ag or generalizable to multiple Ags? 2) Is there a deficiency in the priming of the CD8⁺ T cell compartment of PO mice following an immunizing challenge with LM? We used H-2(d) MHC PO mice to generate CD8⁺ T cell lines individually specific for three known Ags expressed by a recombinant strain of virulent LM. Adoptive transfer experiments into BALB/c host mice revealed that immunity can be mediated by PO CD8⁺ T cells specific for all Ags examined, indicating that perforin-independent immunity is not limited to CD8⁺ T cells that recognize listeriolysin O. Analysis of epitope-specific CD8⁺ T cell expansion by MHC class I tetramer staining and ELISPOT revealed no deficiency in either the primary or secondary response to LM infection in PO mice. These results demonstrate that the perforin-independent pathway of antilisterial resistance mediated by CD8⁺ T cells is generalizable to multiple epitopes. Furthermore, the results show that reduced antilisterial resistance observed with polyclonal PO CD8⁺ T cells is a consequence of a deficiency in effector function and not a result of suboptimal CD8⁺ T cell priming.