Major role for CD8 T cells in the protection against Toxoplasma gondii following dendritic cell vaccination.
Toxoplasma gondii is the causative agent of toxoplasmosis, a worldwide zoonosis for which an effective vaccine is needed. Vaccination with pulsed dendritic cells is very efficient but their use in a vaccination protocol is unconceivable. Nevertheless, unravelling the induced effector mechanisms is crucial to design new vaccine strategies. We vaccinated CBA/J mice with parasite extract-pulsed dendritic cells, challenged them with T. gondii cysts and carried out in vivo depletion of CD4(+) or CD8(+) T lymphocytes to study the subsequent cellular immune response and protective mechanisms. CD4(+) lymphocytes were poorly implicated either in spleen and mesenteric lymph node (MLN) cytokine secretion or in mice protection. By contrast, the increasing number of intracerebral cysts and depletion of CD8(+) cells were strongly correlated, revealing a prominent role for CD8(+) lymphocytes in the protection of mice. Splenic CD8(+) lymphocytes induce a strong Th1 response controlled by a Th2 response whereas CD8(+) cells from MLNs inhibit both Th1 and Th2 responses. CD8(+) cells are the main effectors following dendritic cell vaccination and Toxoplasma infection while CD4(+) T cells only play a minor role. This contrasts with T. gondii infection which elicits the generation of CD4(+) and CD8(+) T cells that provide protective immunity.
Guiton
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R
Université François Rabelais Tours, INRA, UMR 0483 Université-INRA d'Immunologie Parasitaire et Vaccinologie, Biothérapies anti-infectieuses, IFR 136 agents transmissibles en Infectiologie, UFR des Sciences Pharmaceutiques, Tours, France.
Zagani
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R
Dimier-Poisson
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I
D000818:Animals; D001921:Brain / Q000469:parasitology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D008808:Mice, Inbred CBA; D013154:Spleen / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology*; D014611:Vaccination / Q000379:methods*
D016207:Cytokines