CD8 T-cell recognition of macrophages and hepatocytes results in immunity to Listeria monocytogenes

Abstract

CD8 T cells are effective mediators of specific immunity to infection by Listeria monocytogenes, a bacterial pathogen that initially infects macrophages in the spleen and liver and subsequently spreads to hepatocytes and unidentified parenchymal cells in the spleen. To identify the in vivo target cells of L. monocytogenes-immune CD8 T cells, adoptive transfer assays were performed with bone marrow chimeric or transgenic host mice which had been manipulated to alter the major histocompatibility complex molecules expressed on macrophages or hepatocytes. L. monocytogenes-immune CD8 T cells mediate significant immunity in BDF1→β2M-/- chimeras, comparable to that seen in unmanipulated BDF1 recipients. L. monocytogenes-immune CD8 T cells also mediate significant antilisterial immunity in parent→F1 chimeras when the CD8 T cells are syngeneic with the bone marrow donor. These data demonstrate that bone marrow-derived macrophages are major targets for L. monocytogenes-immune CD8 T cells in adoptive transfer assays. Interestingly, significant immunity was observed in parent→F1 chimeras when the L. monocytogenes-immune CD8 T cells were not syngeneic with the bone marrow donor, suggesting that recognition of Listeria-infected non-bone-marrow- derived cells such as hepatocytes may also occur in vivo. Consistent with this possibility, H-2Kb-restricted CD8 T cells specific for the listeriolysin O molecule mediate significant immunity in the liver, but not the spleen, in transgenic mice expressing H-2Kb only on hepatocytes. In addition, Listeria-specific CD8 T cells lyse Listeria-infected hepatocyte- like cells in vitro. Thus, Listeria-infected hepatocytes can be recognized by CD8 T cells in vivo and in vitro.