The induction and kinetics of antigen-specific CD8 T cells are defined by the stage specificity and compartmentalization of the antigen in murine toxoplasmosis.
Toxoplasma gondii forms different life stages, fast-replicating tachyzoites and slow-growing bradyzoites, in mammalian hosts. CD8 T cells are of crucial importance in toxoplasmosis, but it is unknown which parasite stage is recognized by CD8 T cells. To analyze stage-specific CD8 T cell responses, we generated various recombinant Toxoplasma gondii expressing the heterologous Ag beta-galactosidase (beta-gal) and studied whether 1) secreted or cytoplasmic Ags and 2) tachyzoites or bradyzoites, which persist intracerebrally, induce CD8 T cells. We monitored the frequencies and kinetics of beta-gal-specific CD8 T cells in infected mice by MHC class I tetramer staining. Upon oral infection of B6C (H-2(bxd)) mice, only beta-gal-secreting tachyzoites induced beta-gal-specific CD8 T cells. However, upon secondary infection of mice that had received a primary infection with tachyzoites secreting beta-gal, beta-gal-secreting tachyzoites and bradyzoites transiently increased the frequency of intracerebral beta-gal-specific CD8 T cells. Frequencies of splenic and cerebral beta-gal-specific CD8 T cells peaked at day 23 after infection, thereafter persisting at high levels in the brain but declining in the spleen. Splenic and cerebral beta-gal-specific CD8 T cells produced IFN-gamma and were cytolytic upon specific restimulation. Thus, compartmentalization and stage specificity of an Ag determine the induction of CD8 T cells in toxoplasmosis.
Kwok
Lai-Yu
LY
Institut für Medizinische Mikrobiologie und Hygiene, Universitätsklinikum Mannheim, Universität Heidelberg, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany.
Lütjen
Sonja
S
Soltek
Sabine
S
Soldati
Dominique
D
Busch
Dirk
D
Deckert
Martina
M
Schlüter
Dirk
D
D000818:Animals; D030801:Animals, Genetically Modified; D000953:Antigens, Protozoan / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000469:parasitology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005822:Genetic Vectors; D007117:Immunization, Secondary; D007700:Kinetics; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D014122:Toxoplasma / Q000201:enzymology / Q000235:genetics / Q000254:growth & development* / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000201:enzymology / Q000276:immunology* / Q000469:parasitology; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
D000953:Antigens, Protozoan; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D001616:beta-Galactosidase