The flagellar fraction of Trypanosoma cruzi depleted of an immunosuppressive antigen enhances protection to infection and elicits spontaneous T cell responses.
The flagellar fraction (FF) of Trypanosoma cruzi can be separated by immunoaffinity chromatography in two fractions with balanced but opposite immunological effects. The immunoaffinity purified fraction has immunosuppressive activity mediated at least partially by TGF-beta (Hansen et al., submitted). Here we report that the fraction depleted of immunosuppresive antigens (FT) administered with iscom-matrix as adjuvant provides enhanced protection to an infection challenge in immunized mice. In vitro, the FT but not the FF stimulated resident peritoneal cells to produce IL-1 and IL-6. In immunized mice, the FT elicited higher levels of antigen-specific IgG2a than the FF as well as broader recognition of T. cruzi antigens. Splenocytes from mice immunized with FT proliferated spontaneously in vitro and secreted TH1 and TH2 cytokines. The protection provided by FT correlates with its capacity to enhance the secretion of IFN-gamma. We postulate that immunosuppressive antigens present in the FF prevent the development of memory cells secreting IFN-gamma through a TGF-beta dependent mechanism.
Hansen
D S
DS
National Veterinary Institute, Virology Department, Uppsala, Sweden.
Alievi
G
G
Segura
E L
EL
Carlomagno
M
M
Morein
B
B
Villacres-Eriksson
M
M
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000008:administration & dosage* / Q000276:immunology; D014355:Chagas Disease / Q000276:immunology / Q000517:prevention & control; D016207:Cytokines / Q000096:biosynthesis; D005407:Flagella / Q000276:immunology*; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D007166:Immunosuppressive Agents / Q000302:isolation & purification; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D016207:Cytokines; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D015850:Interleukin-6; D007371:Interferon-gamma