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Infection and Immunity, October 2006, p. 5790-5801, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.00098-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Organ- and Disease-Stage-Specific Regulation of Toxoplasma gondii-Specific CD8-T-Cell Responses by CD4 T Cells

Sonja Lütjen,^1, Sabine Soltek,^1, Simona Virna,^1, Martina Deckert,² and Dirk Schlüter^1,3*

Institut für Medizinische Mikrobiologie und Hygiene, Fakultät für klinische Medizin Mannheim der Universität Heidelberg, 68167 Mannheim, Germany,¹ Abteilung für Neuropathologie, Universität zu Köln, 50924 Köln, Germany,² Institut für Medizinische Mikrobiologie, Otto-von-Guericke Universität Magdeburg, 39120 Magdeburg, Germany³

Received 19 January 2006/ Returned for modification 16 March 2006/ Accepted 23 July 2006

Toxoplasma gondii induces a persistent central nervous system infection, which may be lethally reactivated in AIDS patients with low CD4 T-cell numbers. To analyze the role of CD4 T cells for the regulation of parasite-specific CD8 T cells, mice were infected with transgenic T. gondii expressing the CD8 T-cell antigen ß-galactosidase (ß-Gal). Depletion of CD4 T cells prior to infection did not affect frequencies of ß-Gal_876-884-specific (consisting of residues 876 to 884 of ß-Gal) CD8 T cells but resulted in a pronounced reduction of intracerebral ß-Gal-specific gamma interferon (IFN-)-producing and cytolytic CD8 T cells. After cessation of anti-CD4 treatment a normal T. gondii-specific CD4 T-cell response developed, but IFN- production of intracerebral ß-Gal-specific CD8 T cells remained impaired. The important supportive role of CD4 T cells for the optimal functional activity of intracerebral CD8 T cells was also observed in mice that had been depleted of CD4 T cells during chronic toxoplasmosis. Reinfection of chronically infected mice that had been depleted of CD4 T cells during either the acute or chronic stage of infection resulted in an enhanced proliferation of ß-Gal-specific IFN--producing splenic CD8 T cells. However, reinfection of chronically infected mice that had been depleted of CD4 T cells in the acute stage of infection did not reverse the impaired IFN- production of intracerebral CD8 T cells. Collectively, these findings illustrate that CD4 T cells are not required for the induction and maintenance of parasite-specific CD8 T cells but, depending on the stage of infection, the infected organ and parasite challenge infection regulate the functional activity of intracerebral CD8 T cells.

Editor: J. L. Flynn

Present address: Philip Morris Research Laboratories, Köln, Germany.

Present address: Klinische Kooperationseinheit für Dermatoonkologie des Deutschen Krebsforschungszentrums, Klinik für Dermatologie, Allergologie und Venerologie, Universitätsklinikum Mannheim, Mannheim, Germany.

Present address: Abteilung für Klinische Chemie und Molekulare Diagnostik, Biomedizinisches Forschungszentrum, Universität Marburg, Marburg, Germany.