Characterization of the induction of persistent I-A expression by macrophages from Bcgr mice

Peritoneal macrophages from mice that are resistant to Mycobacterium bovis (strain BCG) [Gros et al., J. Immunol. 127,2417, 1981] can be induced to express persistently or transiently major histocompatibility complex (MHC) class II glycoproteins. The induction of persistent expression is dependent on the dose of recombinant interferon-gamma (rIFN-gamma). High doses of rIFN-gamma (100 U) induce persistent Ia expression, whereas lower doses induce only transient Ia expression. Once induced, the persistent expression of Ia does not require its continued synthesis. We show that the expression of Ia by macrophages that transiently express MHC class II glycoproteins is reduced by the addition of cycloheximide or monensin, whereas Ia expression by macrophages that persistently express Ia is not affected. The differential sensitivity of Ia expression to cycloheximide was used to study the induction of persistence that is linked to the Bcg gene. Macrophages were primed with low doses of rIFN-gamma in order to induce transient, cycloheximide-sensitive Ia expression. The cells were then treated with high doses of rIFN-gamma in order to induce persistent, cycloheximide-resistant Ia expression. We found that the induction of persistent Ia expression requires at least 3 hr of exposure to rIFN-gamma. Furthermore, the addition of rIFN-gamma to primed macrophages is followed by a short burst of protein synthesis that is independent of the production of new mRNA. The rapidity with which persistent Ia expression is induced is consistent with the rapid onset of innate resistance to Mycobacterium following injection of BCG.