Internalization of dengue virus-induced suppressor cytokine during transmission of the suppressor signal via macrophage

Abstract

In dengue type 2 virus (DV)-induced suppressor T cell cascade TS1 cells secrete a suppressor cytokine (SF) which acts via syngeneic macrophages (M phi) to recruit TS2 cells. SF binds to both high and low affinity receptors (SF-R) on M phi. In the present study the fate of SF in M phi during transmission of suppressor signal is investigated. It was observed that SF bound to high affinity receptors internalized through receptor mediated endocytosis. This was inhibited by pretreatment of M phi with anti-SF-R-antiserum and didansylcadaverine, a potent inhibitor of endocytosis. Internalized SF was degraded by lysosomal activity as shown by inhibition of suppressor activity by pretreatment of M phi with monensin and NH4Cl. Degraded SF was transported to a site other than SF-R on M phi membrane for recruitment of TS2 cells. This was inhibited by anti-SF-antiserum. Transmission of suppressor signal is inhibited if M phi are treated first with H-2K-mAb and then with SF (shown earlier) but when M phi were treated first with SF and after 1 hr with H-2K-monoclonal antibody, the inhibition did not occur. As SF requires binding to H-2K and SF-R for mediation of suppression, the binding of H-2K occurred with degraded SF within the cell. Thus SF is internalized, degraded and binds to H-2K antigen before its recognition by native T cells.