IMMUNE CD8(-LYMPHOCYTES LYSE LISTERIA MONOCYTOGENES-INFECTED HEPATOCYTES BY A CLASSICAL MHC CLASS I-RESTRICTED MECHANISM() T)

Hepatocytes constitute the principal site of listerial replication in the livers of mice infected i.v. CD8(+) T lymphocytes play a predomina nt role in the host defenses to Listeria monocytogenes. In vitro exper iments by others undertaken to delineate the functions of CD8(+) T lym phocytes have focused primarily on their interaction with Listeria-inf ected macrophages. Such experiments do not address directly the role o f CD8(+) T lymphocytes in eliminating the bulk of Listeria replicating within the liver. Here, we report that immune CD8(+) T cells at an E: T cell ratio greater than or equal to 10:1 lysed Listeria-infected hep atocytes as judged by the following two criteria. Aspartate aminotrans ferase activity in the culture supernatants, indicative of hepatocyte damage, increased significantly, Conversely, infected hepatocytes cocu ltured with immune CD8(+) T cells exhibited a marked reduction in viab le intracellular Listeria assessed by CFUs. Neither immune CD4+T cells nor nonimmune CD8(+) T cells caused a similar increase in aspartate a minotransferase activity released or a decrease in intracellular bacte ria. Immune CD8(+) T cell-mediated lysis of infected hepatocytes was r estricted by classical MHC class I (H-2K(b)) molecules and was inhibit ed by the presence of either brefeldin A or mAb specific for CD8. Thes e results suggest that the predominant role of CD8(+) T lymphocytes in host resistance to listerial infections of the liver may be due to th eir capacity to lyse infected hepatocytes.