An immunoaffinity-purified Trypanosoma cruzi antigen suppresses cellular proliferation through a TGF-β-mediated mechanism

Two subfractions with opposite immunological properties were obtained from the flagellar antigens (FF) of Trypanosoma cruzi epimastigotes by immunoaffinity chromatography. The ligand-bound material (Ag 123) contained four polypeptide bands of 97, 55, 38 and 14 kDa. The nonretained flow- through (FT), induced a potent proliferation of murine naive splenocytes. In contrast, Ag 123 inhibited the proliferative capacity of the FT as well as the proliferation mediated by the mitogen Concanavalin A (Con A). The suppressive effect of Ag 123 on the Con A-mediated proliferation was neutralized by an anti-TGF-β monoclonal antibody. Both Ag 123 and FF stimulated high serum levels of TGF-β in injected mice. Ag 123 also induced in vitro secretion of TGF-β by murine splenocytes. These results demonstrate that Ag 123 is a potent stimulator of TGF-β both in vivo and in vitro. Oligopeptides derived from the 38 kDa protein present in Ag 123 showed homology with human and rat alpha-fetoproteins (AFP). Ag 123 seems to have a key role in the immunosuppression that develops during early stages in the infection with T. cruzi.