Depletion of Regulatory T Cells Augments a Vaccine-Induced T Effector Cell Response against the Liver-Stage of Malaria but Fails to Increase Memory

作者:Mora Maria del Rosario Espinoza*; Steeg Christiane; Tartz Susanne; Heussler Volker; Sparwasser Tim; Link Andreas; Fleischer Bernhard; Jacobs Thomas
来源:PLos One, 2014, 9(8): e104627.
DOI:10.1371/journal.pone.0104627

摘要

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.

  • 出版日期2014-8-12