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 a ll, intracellular pathogens. Previous studies with H-2(b) MHC perforin gene knockout (PO) mice revealed both perforin-dependent and perforin-independe nt pathways of CD8(+) T cell-mediated immunity to Listeria monocytogenes (L M), In this study, we address two previously unresolved issues regarding th e requirement for perforin in antilisterial immunity: 1) Is CD8(+) T cell-m ediated, perforin-independent immunity specific for a single Ag or generali zable 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 spe cific 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, indica ting that perforin-independent immunity is not limited to CD8(+) T cells th at recognize listeriolysin O, Analysis of epitope-specific CD8(+) T cell ex pansion by MHC class I tetramer staining and ELISPOT revealed no deficiency in either the primary or secondary response to LM infection in PO mice. Th ese results demonstrate that the perforin-independent pathway of antilister ial resistance mediated by CD8(+) T cells is generalizable to multiple epit opes, Furthermore, the results show that reduced antilisterial resistance o bserved 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.