AN IMMUNOAFFINITY-PURIFIED TRYPANOSOMA-CRUZI ANTIGEN SUPPRESSES CELLULAR PROLIFERATION THROUGH A TGF-BETA-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) con tained four polypeptide bands of 97, 55, 38 and 14 kDa. The nonretaine d flow-through (FT), induced a potent proliferation of murine naive sp lenocytes. Ln contrast, Ag 123 inhibited the proliferative capacity of the FT as well as the proliferation mediated by the mitogen Concanava lin A (Con A). The suppressive effect of Ag 123 on the Con A-mediated proliferation was neutralized by an anti-TGF-beta monoclonal antibody. Both Ag 123 and FF stimulated high serum levels of TGF-beta in inject ed mice. Ag 123 also induced in vitro secretion of TGF-beta by murine splenocytes. These results demonstrate that Ag 123 is a potent stimula tor of TGF-beta both in vivo and in vitro. Oligopeptides derived from the 38 kDa protein present in Ag 123 showed homology with human and ra t alpha-fetoproteins (AFP). Ag 123 seems to have a key role in the imm unosuppression that develops during early stages in the infection with T. cruzi.