Salmonella typhimurium induces IFN-γ production in murine splenocytes: Role of natural killer cells and macrophages

Lakshmi Ramarathinam, David W. Niesel, Gary R. Klimpel

Research output: Contribution to journalArticlepeer-review

88 Scopus citations


IFN-γ is a cytokine known to play an important role in host defense against Salmonella typhimurium. The lymphoid cells required for in vitro production of IFN-γ after S. typhimurium stimulation of mouse spleen cells was investigated. Spleen cells depleted of cells bearing NK1.1, asialo GM1, Thy 1.2, or CD5 resulted in a significant reduction in IFN-γ production after stimulation with S. typhimurium. In contrast, Con A-induced IFN-γ production was only slightly reduced after depletion of NK1.1- or asialo GM1-bearing cells. Spleen cells from SCID mice produced elevated levels of IFN-γ after stimulation with S. typhimurium. IFN-γ production by SCID spleen cells was dependent upon asialo GM1+ T cells, suggesting that NK cells were the cells producing IFN-γ in response to S. typhimurium. Splenic adherent cells were required for optimal IFN-γ production. However, direct contact between the adherent and nylon wool nonadherent (NWNA) cell populations was not essential. IFN-γ production was observed when the adherent and NWNA cell populations were physically separated or when supernatant from S. typhimurium-stimulated adherent cells was added to NWNA cells. Optimal IFN-γ production was dependent on the presence of TNF-α, inasmuch as addition of antibody to TNF-α to spleen cell or NWNA cell cultures significantly reduced IFN-γ production. However, addition of rTNF-α did not induce IFN-γ production by NWNA cells. These findings document the existence of a T-independent mechanism for early IFN-γ production in response to S. typhimurium, and show that TNF-α is necessary but not sufficient for the production of IFN-γ.

Original languageEnglish (US)
Pages (from-to)3973-3981
Number of pages9
JournalJournal of Immunology
Issue number9
StatePublished - May 1 1993

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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