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) 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-beta monoclonal antibody. Both Ag 123 and FF stimulated high serum levels of TGF-beta in injected mice. Ag 123 also induced in vitro secretion of TGF-beta by murine splenocytes. These results demonstrate that Ag 123 is a potent stimulator 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 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.
Hansen
D S
DS
Instituto Nacional de Diagnóstico e Investigación de la Enfermedad de Chagas Dr Mario Fatala Chaben, Buenos Aires, Argentina.
Villacres-Eriksson
M
M
Akerblom
L
L
Hellman
U
U
Segura
E
E
Carlomagno
M
M
Morein
B
B
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000953:Antigens, Protozoan / Q000032:analysis / Q000494:pharmacology*; D002846:Chromatography, Affinity / Q000379:methods*; D003208:Concanavalin A / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005407:Flagella / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D010447:Peptide Hydrolases; D010455:Peptides / Q000032:analysis; D013154:Spleen / Q000166:cytology; D013347:Subcellular Fractions / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D014349:Trypanosoma cruzi / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D010455:Peptides; D016212:Transforming Growth Factor beta; D003208:Concanavalin A; D010447:Peptide Hydrolases