The Journal of Immunology, Vol 136, Issue 3 963-970, Copyright © 1986 by American Association of Immunologists

ARTICLES

Interferon-gamma induction by lipopolysaccharide: dependence on interleukin 2 and macrophages

DK Blanchard, JY Djeu, TW Klein, H Friedman and WE Stewart 2d

Bacterial lipopolysaccharide (LPS) induced fresh murine splenocytes to produce interferon (IFN)-alpha/beta presumably by stimulation of the B lymphocytes and macrophages. However, when the splenocytes were "aged" for 24 to 72 hr in culture before addition of the LPS, the IFN response was significantly increased and was determined to be predominantly IFN- gamma. Because low levels of interleukin 2 (IL 2) were found to be spontaneously produced by the unstimulated splenocytes during the "aging" process, the effect of IL 2 on IFN induction by LPS in fresh splenocytes was examined. The addition of LPS to freshly prepared splenocyte cultures that were treated with human IL 2, either native or recombinant, before exposure to the LPS resulted in the LPS inducing large amounts of IFN-gamma. IL 2 alone induced little if any IFN in the splenocyte cultures. Depletion of T cells and large granular lymphocytes (LGL) from the cultures by anti-Thy-1.2 antibodies plus complement abrogated IFN-gamma production, and the addition of polymyxin B to "aged" splenocyte cultures resulted in loss of IFN production in response to LPS. Cultures that were enriched for T cells and LGL by passage through nylon wool produced significant amounts of IFN-gamma in response to LPS only if first treated with IL 2. Furthermore, the addition of splenic adherent cells to purified nylon wool-non-adherent (NWNA) cells augmented IFN-gamma production, whether or not the NWNA cells were pretreated with IL 2. This enhancement appeared to require direct contact between adherent cells and NWNA cells, because physical separation abrogated IFN production. The addition of recombinant IL 1 or LPS-conditioned supernatants of macrophage cultures did not replace adherent cell activity. These data demonstrate that LPS, which predominantly induces IFN-alpha/beta in fresh murine splenocytes, is able to stimulate T lymphocytes to produce IFN-gamma if the T cells are first exposed to endogenously produced or exogenously applied IL 2. Because IFN-gamma is a potent activator of the bactericidal and cytocidal potential of macrophages, the induction of IFN-gamma by bacterial LPS may play an important role in resistance/recovery mechanisms against bacterial infections.

This article has been cited by other articles:

				T. H. Wu, C. N. Pabin, Z. Qin, T. Blankenstein, M. Philip, J. Dignam, K. Schreiber, and H. Schreiber Long-Term Suppression of Tumor Growth by TNF Requires a Stat1- and IFN Regulatory Factor 1-Dependent IFN-{gamma} Pathway but Not IL-12 or IL-18 J. Immunol., March 1, 2004; 172(5): 3243 - 3251. [Abstract] [Full Text] [PDF]

				M. Watanabe and M. Nagai Reciprocal Protective Immunity against Bordetella pertussis and Bordetella parapertussis in a Murine Model of Respiratory Infection Infect. Immun., November 1, 2001; 69(11): 6981 - 6986. [Abstract] [Full Text] [PDF]

				M. Galdiero, M. D'Amico, F. Gorga, C. Di Filippo, M. D'Isanto, M. Vitiello, A. Longanella, and A. Tortora Haemophilus influenzae Porin Contributes to Signaling of the Inflammatory Cascade in Rat Brain Infect. Immun., January 1, 2001; 69(1): 221 - 227. [Abstract] [Full Text] [PDF]

				T. Mattern, G. Girroleit, H.-D. Flad, E. T. Rietschel, and A. J. Ulmer CD34+ Hematopoietic Stem Cells Exert Accessory Function in Lipopolysaccharide-induced  T Cell Stimulation and CD80 Expression on Monocytes J. Exp. Med., February 15, 1999; 189(4): 693 - 700. [Abstract] [Full Text] [PDF]