title: The application of anti-Toso antibody enhances CD8(+) T cell responses in experimental malaria vaccination and disease.
abstract: Toso is a molecule highly expressed on B cells. It influences their survival and was identified as an IgM binding molecule. B cells and natural antibodies play a role in vaccination-induced CD8(+) T cell responses. We investigated the impact of an anti-Toso antibody on vaccination efficiency in a malaria vaccination model. In this model, CD8(+) T cells exert antiparasitic functions on infected hepatocytes in the liver stage of the disease. In vaccinated anti-Toso treated mice, more antigen-specific CD8(+) T cells were induced than in control mice and after infection with Plasmodium berghei ANKA (PbA) sporozoites, the liver parasite burden was lower. In B cell deficient mice, the anti-Toso antibody did not stimulate the CD8(+) T cell response, indicating that B cells were mediating this effect. Furthermore, we analyzed the influence of anti-Toso treatment on non-vaccinated mice in the PbA infection model, in which CD8(+) T cells cause brain pathology. Anti-Toso treatment increased cerebral pathology and the accumulation of CD8(+) T cells in the brain. Thus, anti-Toso treatment enhanced the CD8(+) T cell response against PbA in a vaccination and in an infection model. Our findings indicate that Toso may be a novel target to boost vaccine-induced CD8(+) T cell responses.
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Straße 74, 20359 Hamburg, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Lapke
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Straße 74, 20359 Hamburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Tartz
authors.affiliation: Institute for Clinical Chemistry and Inflammation Research, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
authors.forename: Kyeong-Hee
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Straße 74, 20359 Hamburg, Germany. Electronic address: tjacobs@bni-hamburg.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000008:administration & dosage*; D001921:Brain / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D008099:Liver / Q000469:parasitology; D008288:Malaria / Q000517:prevention & control* / Q000628:therapy*; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D059208:Parasite Load; D010962:Plasmodium berghei / Q000302:isolation & purification
chemical_list: D001323:Autoantibodies; D002352:Carrier Proteins; C499656:Fcmr protein, mouse; D017780:Malaria Vaccines; D008565:Membrane Proteins
keywords: B cells; CD8(+) T cells; Malaria; Toso; Vaccination