HEPATOCYTES CAN SERVE AS ACCESSORY CELLS IN THE RESPONSE OF IMMUNE T-LYMPHOCYTES TO HEAT-KILLED LISTERIA-MONOCYTOGENES

Previous findings in our laboratory indicated that the bulk of Listeri a monocytogenes injected intravenously into mice and recovered in the liver is taken up and replicates within hepatocytes. Other investigato rs have shown that hepatocytes can display costimulatory adhesion mole cules, express major histocompatibility complex class I and II molecul es, and secrete a number of cytokines, including interleukin-1 (IL-1), IL-6, and IL-8. These data suggest that hepatocytes may serve as acce ssory cells in the immune response to L. monocytogenes. The accessory function and capacity of hepatocytes to present listerial antigens, ho wever, have never been explored. We undertook a series of experiments to examine the response of Listeria-immune T lymphocytes to murine hep atocytes preincubated with heat-killed listeriae (HKL). Electron micro graphs showing the organism within membrane-limiting vacuoles demonstr ated the capacity of hepatocytes to internalize Hl[a. T cells cocultur ed,vith hepatocytes pulsed with HKL exhibited a 5- to 10-fold increase in [methyl-H-3]thymidine incorporation relative to T cells cultured w ith either hepatocytes or HKL alone. Similarly, gamma interferon produ ction by immune T cells was elevated significantly in cultures that co ntained both hepatocytes and HKL. The optimal response of T cells requ ired lysosomal processing of HKL by hepatocytes and contact between th e 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, thes e endings demonstrate that hepatocytes pulsed with HKL can stimulate t he antigen-specific response of immune T lymphocytes. These results su ggest that hepatocytes can serve as accessory cells in host defenses t o listerial infections of the liver.