EARLY GAMMA INTERFERON-PRODUCTION BY NATURAL-KILLER-CELLS IS IMPORTANT IN DEFENSE AGAINST MURINE LISTERIOSIS

A spot enzyme-linked immunosorbent assay was used to show that subcutaneous inoculation of a sublethal number of Listeria monocytogenes resulted in the early appearance of gamma interferon (IFN-gamma)-producing cells in the draining lymph nodes. In contrast, inoculation of UV-killed L. monocytogenes failed to cause the appearance of IFN-gamma-producing cells. The appearance of IFN-gamma-secreting cells in response to the living organisms peaked at 24 h of infection and then declined. The draining lymph node cells responsible for secreting IFN-gamma belonged to a cell population that was positive for the NK1.1, asialo-GM-1, and Thy-1 markers but negative for the CD4 and CD8 T cell subset markers. Early elimination of natural killer (NK) cells by treatment with anti-NK cell antibodies resulted in severe exacerbation of infection, as did early neutralization of endogenous IFN-gamma by treatment with a rat anti-murine IFN-gamma monoclonal antibody. In contrast, depletion of CD4+ and CD8+ T cells failed to exacerbate infection. The results serve to show that the early production of IFN-gamma by NK cells, rather than by T cells, is an essential event in resistance to listeriosis.