Immune CD8+ T lymphocytes lyse Listeria monocytogenes-infected hepatocytes by a classical MHC class I-restricted mechanism.
Hepatocytes constitute the principal site of listerial replication in the livers of mice infected i.v. CD8+ T lymphocytes play a predominant role in the host defenses to Listeria monocytogenes. In vitro experiments by others undertaken to delineate the functions of CD8+ T lymphocytes have focused primarily on their interaction with Listeria-infected macrophages. Such experiments do not address directly the role of 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 > or = 10:1 lysed Listeria-infected hepatocytes as judged by the following two criteria. Aspartate aminotransferase activity in the culture supernatants, indicative of hepatocyte damage, increased significantly. Conversely, infected hepatocytes cocultured with immune CD8+ T cells exhibited a marked reduction in viable intracellular Listeria assessed by CFUs. Neither immune CD4+ T cells nor nonimmune CD8+ T cells caused a similar increase in aspartate aminotransferase activity released or a decrease in intracellular bacteria. Immune CD8+ T cell-mediated lysis of infected hepatocytes was restricted by classical MHC class I (H-2Kb) molecules and was inhibited by the presence of either brefeldin A or mAb specific for CD8. These results suggest that the predominant role of CD8+ T lymphocytes in host resistance to listerial infections of the liver may be due to their capacity to lyse infected hepatocytes.
Jiang
X
X
Department of Medicine, University of Pittsburgh Medical Center, PA 15213, USA.
Gregory
S H
SH
Wing
E J
EJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D020126:Brefeldin A; D016827:CD8 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D003517:Cyclopentanes / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005260:Female; D006183:H-2 Antigens / Q000235:genetics*; D008089:Listeria monocytogenes / Q000276:immunology* / Q000302:isolation & purification* / Q000472:pathogenicity; D008099:Liver / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D018942:Macrolides; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D016827:CD8 Antigens; D003517:Cyclopentanes; D006183:H-2 Antigens; D018942:Macrolides; D020126:Brefeldin A