Hepatocytes can serve as accessory cells in the response of immune T lymphocytes to heat-killed Listeria monocytogenes

Abstract

Previous findings in our laboratory indicated that the bulk of Listeria monocytogenes injected intravenously into mice and recovered in the liver is taken up and replicates within hepatocytes. Other investigators have shown that hepatocytes can display costimulatory adhesion molecules, express major histocompatibility complex class I and II molecules, and secrete a number of cytokines, including interleukin-1 (IL-1), IL-6, and IL-8. These data suggest that hepatocytes may serve as accessory cells in the immune response to L. monocytogenes. The accessory function and capacity of hepatocytes to present listerial antigens, however, have never been explored. We undertook a series of experiments to examine the response of Listeria-immune T lymphocytes to murine hepatocytes preincubated with heat-killed listeriae (HKL). Electron micrographs showing the organism within membrane-limiting vacuoles demonstrated the capacity of hepatocytes to internalize HKL. T cells cocultured with hepatocytes pulsed with HKL exhibited a 5- to 10-fold increase in [methyl-3H]thymidine incorporation relative to T cells cultured with either hepatocytes or HKL alone. Similarly, gamma interferon production by immune T cells was elevated significantly in cultures that contained both hepatocytes and HKL. The optimal response of T cells required lysosomal processing of HKL by hepatocytes and contact between the two cell populations. Furthermore, maximum T-cell proliferation and gamma interferon production were dependent upon the presence of CD4+ T lymphocytes and the expression of Ia antigens. Taken together, these findings demonstrate that hepatocytes pulsed with HKL can stimulate the antigen-specific response of immune T lymphocytes. These results suggest that hepatocytes can serve as accessory cells in host defenses to listerial infections of the liver.