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Infection and Immunity, January 2003, p. 309-316, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.309-316.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

A GRA1 DNA Vaccine Primes Cytolytic CD8⁺ T Cells To Control Acute Toxoplasma gondii Infection

T. Scorza,^* S. D'Souza, M. Laloup, J. Dewit, J. De Braekeleer, H. Verschueren,^|| M. Vercammen,^# K. Huygen, and E. Jongert

Department of Toxoplasmosis, Pasteur Institute of Brussels, 1180 Brussels, Belgium

Received 2 June 2002/ Returned for modification 27 July 2002/ Accepted 4 October 2002

Protective immunity against Toxoplasma gondii is known to be mediated mainly by T lymphocytes and gamma interferon (IFN-). 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- 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.

Editor: W. A. Petri, Jr.

Present address: Institute of Parasitology, McGill University, Ste-Anne-de-Belle-Vue, H9X 3V9 Montreal, Quebec, Canada.

Present address: Laboratory of Mycobacterial Immunology, Pasteur Institute of Brussels, Brussels, Belgium.

Present address: Laboratory of Toxoplasmosis, Pasteur Institute of Brussels, Brussels, Belgium.

^|| Present address: Department of Molecular Biology, Flanders Interuniversity Institute of Biotechnology, University of Ghent, Ghent, Belgium.

^# Present address: Department of Clinical Chemistry, Academic Hospital of the Free University of Brussels, Brussels, Belgium.

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