title: Depletion of regulatory T cells augments a vaccine-induced T effector cell response against the liver-stage of malaria but fails to increase memory.
abstract: Regulatory T cells (T(reg)) have been shown to restrict vaccine-induced T cell responses in different experimental models. In these studies CD4(+)CD25(+) T(reg) were depleted using monoclonal antibodies against CD25, which might also interfere with CD25 on non-regulatory T cell populations and would have no effect on Foxp3(+)CD25(-) T(reg). To obtain more insights in the specific function of T(reg) during vaccination we used mice that are transgenic for a bacterial artificial chromosome expressing a diphtheria toxin (DT) receptor-eGFP fusion protein under the control of the foxp3 gene locus (depletion of regulatory T cell mice; DEREG). As an experimental vaccine-carrier recombinant Bordetella adenylate cyclase toxoid fused with a MHC-class I-restricted epitope of the circumsporozoite protein (ACT-CSP) of Plasmodium berghei (Pb) was used. ACT-CSP was shown by us previously to introduce the CD8+ epitope of Pb-CSP into the MHC class I presentation pathway of professional antigen-presenting cells (APC). Using this system we demonstrate here that the number of CSP-specific T cells increases when T(reg) are depleted during prime but also during boost immunization. Importantly, despite this increase of T effector cells no difference in the number of antigen-specific memory cells was observed.
authors.affiliation: Bernhard Nocht Institut für Tropenmedizin, Abteilung Immunologie, Hamburg, Germany; Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg, Germany.
authors.forename: Maria del Rosario
authors.initials: MR
authors.lastname: Espinoza Mora
authors.affiliation: Bernhard Nocht Institut für Tropenmedizin, Abteilung Immunologie, Hamburg, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Steeg
authors.affiliation: Bernhard Nocht Institut für Tropenmedizin, Abteilung Immunologie, Hamburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Tartz
authors.affiliation: Bernhard Nocht Institut für Tropenmedizin, Abteilung Immunologie, Hamburg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Heussler
authors.affiliation: TWINCORE, Zentrum für Experimentelle und Klinische Infektionsforschung, Institut für Infektionsimmunologie, Hannover, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
authors.affiliation: Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Link
authors.affiliation: Bernhard Nocht Institut für Tropenmedizin, Abteilung Immunologie, Hamburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Fleischer
authors.affiliation: Bernhard Nocht Institut für Tropenmedizin, Abteilung Immunologie, Hamburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D007114:Immunization; D007117:Immunization, Secondary; D007156:Immunologic Memory; D008099:Liver / Q000469:parasitology*; D008212:Lymphocyte Depletion; D008288:Malaria / Q000469:parasitology* / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000276:immunology*; D008297:Male; D051379:Mice; D010962:Plasmodium berghei / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D017780:Malaria Vaccines