Nonspecific Regulatory Mechanism of Contact Sensitivity: Nonspecific Suppressor Factor Suppresses the Antigen-Presenting Activity of Dendritic Cells to Induce Contact Sensitivity

Abstract

Nonspecific suppressor factor (NSF), which inhibits the passive transfer of contact sensitivity (CS), is produced from macrophage-like cells induced by oxazolone-conjugated spleen cells. NSF binds selectively to 1a-positive, cyclophosphamide-sensitive, and plastic-adherent non-T cells (named intermediate cells) present in the spleen. NSF-treated intermediate cells acquire the ability to suppress the passive transfer of CS nonspecifically. Because the phenotype of the intermediate cells is similar to that of antigen-presenting cells (APC) of macrophage lineage, we examined the effect of NSF on APC. NSF suppressed the APC activity of draining lymph node cells from mice sensitized with fluorescein isothiocyanate or picryl chloride (FITC-LNC or TNP-LNC) to induce CS. Suppressor molecules which suppress the passive transfer of CS and the APC activity were recovered in the same fraction around 43 kDa by dye-affinity and gel chromatography purification. The results that the suppressor activity of NSF was absorbed with lymph node cells or FITC-LNC, but not 33D1 or anti-1a monoclonal antibody plus complement-treated FITC-LNC indicated that NSF reacts directly with antigen-bearing dendritic cells in the draining lymph node. In contrast with spleen cells, lymph node cells did not have the intermediate function, i.e., NSF-treated LNC could not suppress the passive transfer of CS nor the ability of FITC-LNC to induce CS (APC activity). NSF still blocks the ability of FITC-LNC to induce CS after treatment with cyclophosphamide. Thus, the lymph node and spleen include distinct functional cell populations which express 1a antigen and interact with NSF. APC in the draining lymph node are downregulated directly by NSF and the intermediate cells in the spleen play a modulatory role in the suppressor pathway of NSF.