title: A GRA1 DNA vaccine primes cytolytic CD8(+) T cells to control acute Toxoplasma gondii infection.
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.
authors.affiliation: Department of Toxoplasmosis, Pasteur Institute of Brussels, 1180 Brussels, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: Scorza
authors.forename: S
authors.initials: S
authors.lastname: D'Souza
authors.forename: M
authors.initials: M
authors.lastname: Laloup
authors.forename: J
authors.initials: J
authors.lastname: Dewit
authors.forename: J
authors.initials: J
authors.lastname: De Braekeleer
authors.forename: H
authors.initials: H
authors.lastname: Verschueren
authors.forename: M
authors.initials: M
authors.lastname: Vercammen
authors.forename: K
authors.initials: K
authors.lastname: Huygen
authors.forename: E
authors.initials: E
authors.lastname: Jongert
mesh_terms: D000208:Acute Disease; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001921:Brain / Q000469:parasitology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D016052:Protozoan Vaccines / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology* / Q000472:pathogenicity; D014124:Toxoplasmosis, Animal / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; C412913:GRA1 antigen; D016052:Protozoan Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma