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Vaccine. 2015 Nov 27;33(48):6763-70. doi: 10.1016/j.vaccine.2015.10.065. Epub 2015 Oct 25.

The application of anti-Toso antibody enhances CD8(+) T cell responses in experimental malaria vaccination and disease.

Author information

1
Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Straße 74, 20359 Hamburg, Germany.
2
Institute for Clinical Chemistry and Inflammation Research, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
3
Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Straße 74, 20359 Hamburg, Germany. Electronic address: tjacobs@bni-hamburg.de.

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.

KEYWORDS:

B cells; CD8(+) T cells; Malaria; Toso; Vaccination

PMID:
26597034
DOI:
10.1016/j.vaccine.2015.10.065
[Indexed for MEDLINE]

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