Characterization of the Induction of Persistent I‐A Expression by Macrophages From Bcg r 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‐γ (rlFN‐γ). High doses of rlFN‐γ (100 U) induce persistent la expression, whereas lower closes induce only transient la expression. Once induced, the persistent expression of la does not require its continued synthesis. We show that the expression of la by macrophages that transiently express MHC class II glycoproteins is reduced by the addition of cycloheximide or monensin, whereas la expression by macrophages that persistently express la is not affected. The differential sensitivity of la 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 rlFN‐γ in order to induce transient, cycloheximide‐sensitive la expression. The cells were then treated with high doses of rlFN‐γ in order to induce persistent, cycloheximide‐resistant la expression. We found that the induction of persistent la expression requires at least 3 hr of exposure to rlFN‐γ. Furthermore, the addition of rlFN‐γ 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 la expression is induced is consistent with the rapid onset of innate resistance to Mycobacterium following injection of BCG.