Accessory function of Kupffer cells in the antigen-specific blastogenic response of an L3T4+ T-lymphocyte clone to Listeria monocytogenes

Abstract

The function of Kupffer cells in the development of protective immunity to infection by Listeria monocytogenes is controversial. To determine their role in antilisterial host defenses, Kupffer cells were separated from other nonparenchymal cells of the liver by centrifugation on a metrizamide gradient followed by adherence to glass or plastic. The resultant highly enriched Kupffer cell population supported the antigen-specific blastogenic response [( 3H]thymidine incorporation) of cloned L3T4+ T lymphocytes to L. monocytogenes in vitro. Blastogenesis was dependent upon the duration of the incubation period, the concentration of the antigen, and the number of Kupffer cells in culture. Maximum reactivity was greater than that observed when the same T-cell population was incubated with adherent peritoneal exudate cells and antigen under optimal conditions. The addition of antibodies specific for murine interleukin-1 beta to cocultures of Kupffer cells and T lymphocytes eliminated the antigen-stimulated incorporation of [3H]thymidine, indicating a requirement for interleukin-1. Analysis of the culture supernatants demonstrated that, in addition to interleukin-1, granulocyte-macrophage colony-stimulating factor, interleukin-6, and gamma interferon were elaborated in cocultures containing cloned T lymphocytes, Kupffer cells, and antigen. These results suggest that Kupffer cells may serve a critical role in the development of immunity to infection by L. monocytogenes in vivo.