Organ- and disease-stage-specific regulation of Toxoplasma gondii-specific CD8-T-cell responses by CD4 T cells.
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 beta-galactosidase (beta-Gal). Depletion of CD4 T cells prior to infection did not affect frequencies of beta-Gal(876-884)-specific (consisting of residues 876 to 884 of beta-Gal) CD8 T cells but resulted in a pronounced reduction of intracerebral beta-Gal-specific gamma interferon (IFN-gamma)-producing and cytolytic CD8 T cells. After cessation of anti-CD4 treatment a normal T. gondii-specific CD4 T-cell response developed, but IFN-gamma production of intracerebral beta-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 beta-Gal-specific IFN-gamma-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-gamma 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.
Lütjen
Sonja
S
Institut für Medizinische Mikrobiologie, Otto-von-Guericke Universität Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
Soltek
Sabine
S
Virna
Simona
S
Deckert
Martina
M
Schlüter
Dirk
D
D000818:Animals; D001921:Brain / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008815:Mice, Inbred Strains; D013154:Spleen / Q000276:immunology*; D014122:Toxoplasma; D014124:Toxoplasmosis, Animal / Q000276:immunology*
D007371:Interferon-gamma