Multidimensional analyses of proinsulin peptide-specific regulatory T cells induced by tolerogenic dendritic cells

Jessica S. Suwandi, Sandra Laban, Kincsὅ Vass, Antoinette Joosten, Vincent van Unen, Boudewijn Lelieveldt, Thomas Höllt, Jaap Jan Zwaginga, Tatjana Nikolic, Bart O. Roep

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Abstract

Induction of antigen-specific regulatory T cells (Tregs) in vivo is the holy grail of current immune-regulating therapies in autoimmune diseases, such as type 1 diabetes. Tolerogenic dendritic cells (tolDCs) generated from monocytes by a combined treatment with vitamin D and dexamethasone (marked by CD52hi and CD86lo expression) induce antigen-specific Tregs. We evaluated the phenotypes of these Tregs using high-dimensional mass cytometry to identify a surface-based T cell signature of tolerogenic modulation. Naïve CD4+ T cells were stimulated with tolDCs or mature inflammatory DCs pulsed with proinsulin peptide, after which the suppressive capacity, cytokine production and phenotype of stimulated T cells were analysed. TolDCs induced suppressive T cell lines that were dominated by a naïve phenotype (CD45RA+CCR7+). These naïve T cells, however, did not show suppressive capacity, but were arrested in their naïve status. T cell cultures stimulated by tolDC further contained memory-like (CD45RA-CCR7-) T cells expressing regulatory markers Lag-3, CD161 and ICOS. T cells expressing CD25lo or CD25hi were most prominent and suppressed CD4+ proliferation, while CD25hi Tregs also effectively supressed effector CD8+ T cells. We conclude that tolDCs induce antigen-specific Tregs with various phenotypes. This extends our earlier findings pointing to a functionally diverse pool of antigen-induced and specific Tregs and provides the basis for immune-monitoring in clinical trials with tolDC.

Original languageEnglish
Article number102361
Pages (from-to)1-11
Number of pages11
JournalJournal of Autoimmunity
Volume107 (2020)
DOIs
Publication statusPublished - 2019

Keywords

  • Immune therapy
  • Mass cytometry
  • Regulatory T cells
  • Tolerogenic dendritic cells

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    Suwandi, J. S., Laban, S., Vass, K., Joosten, A., van Unen, V., Lelieveldt, B., Höllt, T., Zwaginga, J. J., Nikolic, T., & Roep, B. O. (2019). Multidimensional analyses of proinsulin peptide-specific regulatory T cells induced by tolerogenic dendritic cells. Journal of Autoimmunity, 107 (2020), 1-11. [102361]. https://doi.org/10.1016/j.jaut.2019.102361