Major role for CD8+ T cells in the protection against Toxoplasma gondii following dendritic cell vaccination

Abstract

Summary 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. © 2009 Blackwell Publishing Ltd.