Regulation of gamma interferon production by natural killer cells in scid mice: Roles of tumor necrosis factor and bacterial stimuli

Research output: Contribution to journalArticlepeer-review

172 Scopus citations

Abstract

CB-17 scid mice exhibit a T-cell-independent but gamma interferon (IFN-γ)-dependent immunity to Listeria monocytogenes. In this study, we analyzed the specific cellular interactions involved in this process. scid mouse-derived natural killer (NK) cells cultured with heat-killed (HK) L. monocytogenes and macrophages secreted IFN-γ. No IFN-γ was produced in cultures containing HK L. monocytogenes but lacking macrophages. However, medium derived from macrophages incubated with HK L. monocytogenes or other microorganisms stimulated IFN-γ production by isolated NK cells. Treatment of macrophage-conditioned supernatants with neutralizing monoclonal anti-tumor necrosis factor (TNF) significantly reduced their capacity to stimulate NK cells to produce IFN-γ. Yet, purified recombinant TNF-α by itself was unable to stimulate NK cells. Thus, TNF was necessary but not sufficient to induce maximal IFN-γ production by NK cells. Sonicated L. monocytogenes stimulated production of IFN-γ by NK cells that was resistant to anti-TNF. Stimulation was markedly enhanced by the addition of recombinant TNF-α. These studies demonstrated that activation of scid NK cells for secretion of IFN-γ requires two signals: TNF-α and a second product which may be of bacterial origin and may require processing by mononuclear phagocytes. We suggest that the T-cell-independent production of IFN-γ by NK cells provides the host with a rapid mechanism to temporarily heighten nonspecific resistance to infection until such time as T-cell-dependent sterilizing immune responses can be generated.

Original languageEnglish
Pages (from-to)1709-1715
Number of pages7
JournalInfection and immunity
Volume59
Issue number5
StatePublished - 1991

Fingerprint

Dive into the research topics of 'Regulation of gamma interferon production by natural killer cells in scid mice: Roles of tumor necrosis factor and bacterial stimuli'. Together they form a unique fingerprint.

Cite this