1989 Volume 64 Issue 8 Pages 499-509
Staphylococcal enterotoxin A (SEA), a T cell mitogen, was found to induce a high levelof interferon r (IFN-r) in mice which had been immunized with killed Bacillus Calmette Guerin (BCG) in water-in-oil-in-water (W/O/W) emulsion.
The phenomenon wasanalysed by in vivo and in vitro experiments, and the following results were obtained.
1. The SEA-induced IFN was inactivated by treatment with 0.2M glycine-HC1 (pH 2.0) but not by heating at 56° for 30 min. nor by treatment with anti-IFN a/18 antibodies, and the fact suggest that the IFN belonged to they type.
2. Treatment of the BCG-sensitized mice with silica and 2-chloroadenosine (2CA), specificlethal agents for macrophages, reduced the SEA-induced IFN production.
3. The SEA-induced IFN production occurred in mice immunized with BCG eitherintravenously or intraperitoneally, although they showed weak or no footpad reactionto purified protein derivatives (PPD).
In contrast, mice sensitized subcutaneously with BCG showed strong foodpad reaction to PPD but not the SEA-induced IFN production.
Thus, the mere presence of BCG-sensitized T cells does not appear to result in the SEA-indused IFN production.
4. In vitro experiments, in which SEA-induced IFN production was determined in theculture of BCG-sensitized spleen cells, showed that principal IFN-producing cells were Lyt-1+T cells.
5. Deprivation of macrophages from BCG-sensitized spleen cell population by passingthrough Sephadex G-10 column reduced the SEA-induced IFN production in the culture.
Addition of 2CA to the culture medium also reduced the SEA-induced IFN productionby the BCG-sensitized spleen cells.
6. The SEA-induced IFN production in the culture of the BCG-sensitized spleen cellswas suppressed in the presence of lipoxygenase inhibitor, i. e., caffeic acid ornordihydroguaiaretic acid.
7. The plastic adherent spleen cells (i. e. macrophages) from mice sensitized with BCG produced leukotriene C4 (LTC4).
The suppression of the SEA-induced IFN productionof BCG-sensitized spleen cells in the presence of the lipoxygenase in hibitor wasprevented by addition of synthetic LTC4.
These results suggest that LTC4 released from macrophages activated by BCG causesproduction of IFN by BCG-sensitized T cells responding to SEA.
