Trypanosoma Cruzi: Protective Immunity in Mice Immunized With Paraflagellar Rod Proteins Is Associated With a T-helper Type 1 Response

Exp Parasitol. 1996 Nov;84(2):156-67. doi: 10.1006/expr.1996.0101.

Abstract

We have examined the ability of mice to survive a lethal challenge with the parasitic hemoflagellate, Trypanosoma cruzi, following immunization with paraflagellar rod proteins (PAR) 1 and 2 either alone or in combination with the following adjuvants: Freund's, alum, QS-21, Ribi-700, or IL-12. PAR administered subcutaneously (sc) in combination with Freund's or alum provided significant protection, 100 and 83%, respectively, against a T. cruzi challenge. In contrast, PAR in combination with QS-21, Ribi-700, IL-12, or Freund's administered intraperitoneally (ip) or PAR alone provide no protection against a challenge. PAR-specific serum antibody titers and isotype profiles for several of the immunization regimens were determined, and no positive correlation could be seen between a protective immune response and either antibody titer or the subclass of antibody induced. We also examined the ability of PAR to stimulate T cells from the spleen and lymph nodes of mice immunized with PAR in combination with Freund's (sc), Freund's (ip), alum, or Ribi-700. Each of the adjuvants strongly enhanced the ability of enriched T cells to proliferate in a PAR-specific fashion, suggesting no obvious correlation between PAR-specific T cell activation and protection. However, examination of the cytokine profiles of the stimulated T cell groups showed that the protective groups differed from the nonprotective groups. While all four groups showed low levels of IL-10, the Freund's (sc) and alum groups had higher levels of IFN-gamma and IL-2 than Freund's (ip) and Ribi-700 groups, and most strikingly, no IL-4 could be detected in either the Freund's (sc) or the alum group, in contrast to significant levels of IL-4 in both the Freund's (ip) and the Ribi-700 group. These findings indicate that protective immunity in mice immunized with PAR is associated with a Th1-type response.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antibodies, Protozoan / blood
  • Chagas Disease / immunology*
  • Chagas Disease / parasitology
  • Female
  • Immunity, Active
  • Immunization Schedule
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Interferon-gamma / biosynthesis
  • Interleukins / biosynthesis
  • Mice
  • Mice, Inbred BALB C
  • Parasitemia / immunology
  • Protozoan Proteins / immunology*
  • Protozoan Vaccines / immunology*
  • Th1 Cells / immunology*
  • Trypanosoma cruzi / immunology*
  • Vaccination

Substances

  • Adjuvants, Immunologic
  • Antibodies, Protozoan
  • Immunoglobulin G
  • Immunoglobulin M
  • Interleukins
  • Protozoan Proteins
  • Protozoan Vaccines
  • paraflagellar rod proteins, Trypanosoma brucei
  • PAR 2 protein, Trypanosoma cruzi
  • Interferon-gamma