Depletion of regulatory T cells augments a vaccine-induced T effector cell response against the liver-stage of malaria but fails to increase memory

PLoS One. 2014 Aug 12;9(8):e104627. doi: 10.1371/journal.pone.0104627. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Immunization
  • Immunization, Secondary
  • Immunologic Memory*
  • Liver / parasitology*
  • Lymphocyte Depletion
  • Malaria / parasitology*
  • Malaria / prevention & control*
  • Malaria Vaccines / immunology*
  • Male
  • Mice
  • Plasmodium berghei / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Malaria Vaccines

Grant support

This work was supported by a Grant of the German Research Foundation (SFB 841) to T.J. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.