A GRA1 DNA vaccine primes cytolytic CD8(+) T cells to control acute Toxoplasma gondii infection

Infect Immun. 2003 Jan;71(1):309-16. doi: 10.1128/IAI.71.1.309-316.2003.

Abstract

Protective immunity against Toxoplasma gondii is known to be mediated mainly by T lymphocytes and gamma interferon (IFN-gamma). The contribution of CD4(+) and CD8(+) T-lymphocyte subsets to protective immune responses against T. gondii infection, triggered by a GRA1 (p24) DNA vaccine, was assessed in this study. In vitro T-cell depletion experiments indicated that both CD4(+) and CD8(+) T-cell subsets produced IFN-gamma upon restimulation with a T. gondii lysate. In addition, the GRA1 DNA vaccine elicited CD8(+) T cells that were shown to have cytolytic activity against parasite-infected target cells and a GRA1-transfected cell line. C3H mice immunized with the GRA1 DNA vaccine showed 75 to 100% protection, while 0 to 25% of the mice immunized with the empty control vector survived challenge with T. gondii cysts. In vivo T-cell depletion experiments indicated that CD8(+) T cells were essential for the survival of GRA1-vaccinated C3H mice during the acute phase of T. gondii infection, while depletion of CD4(+) T cells led to an increase in brain cyst burden during the chronic phase of infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Antigens, Protozoan / genetics
  • Antigens, Protozoan / immunology*
  • Antigens, Protozoan / metabolism
  • Brain / parasitology
  • CD4-Positive T-Lymphocytes / immunology
  • Female
  • Humans
  • Interferon-gamma / biosynthesis
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C3H
  • Protozoan Vaccines / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Toxoplasma / immunology*
  • Toxoplasma / pathogenicity
  • Toxoplasmosis, Animal / immunology
  • Toxoplasmosis, Animal / prevention & control*
  • Vaccination
  • Vaccines, DNA / immunology*

Substances

  • Antigens, Protozoan
  • GRA1 antigen
  • Protozoan Vaccines
  • Vaccines, DNA
  • Interferon-gamma