Nonspecific regulatory mechanism of contact sensitivity: nonspecific suppressor factor (NSF)-treated intermediate cells produce a second nonspecific suppressor factor (NSFint).

Nonspecific suppressor factor (NSF), which inhibits the passive transfer of contact sensitivity (CS), is produced spontaneously from macrophage-like suppressor cells induced by intravenous administration of oxazolone (Ox)-conjugated spleen cells. NSF binds selectively to Ia-positive, cyclophosphamide (CY)-sensitive, and plastic-adherent cells (named intermediate cells) present in the normal spleen. NSF-treated intermediate cells acquire the ability to suppress the passive transfer of CS nonspecifically. In this study, NSF-treated intermediate cells were found to release a second nonspecific suppressor factor (NSFint) during a 2-hr culture, while retaining their suppressor activity. Investigation of the relationship between these two factors showed that both NSF and NSFint were trypsin-sensitive, nondialyzable proteins. However, gel chromatography revealed that NSF was about 43 kDa, while NSFint was about 20 kDa. NSF was released from macrophage-like suppressor cells after RNA-dependent protein synthesis. In contrast, production of NSFint was energy dependent but did not require protein synthesis. Intermediate cells pretreated with lysosomotropic agents, such as ammonium chloride or chloroquine, did not acquire suppressor activity nor release suppressor factors due to NSF treatment. These observations suggest that NSFint is an altered form of NSF released by the intermediate after having undergone some modification; the biochemical mechanism is not known. This study showed that the intermediate cells play an active role in the suppressor cascade of NSF.