Reduced PD-1 expression on circulating follicular and conventional FOXP3+ Treg cells in children with new onset type 1 diabetes and autoantibody-positive at-risk children

Andrea Vecchione, Roberta Di Fonte, Jolanda Gerosa, Tatiana Jofra, Maria Pia Cicalese, Vincenzo Napoleone, Elio Ippolito, Giuseppe Galvani, Francesca Ragogna, Angela Stabilini, Eleonora Bianconi, Pauline Grogan, Clara Bonura, Riccardo Bonfanti, Giulio Frontino, Rita Nano, Raffaela Melzi, Maurizio De Pellegrin, Andrea Laurenzi, Franco MeschiGraziano Barera, Andrea Rigamonti, Rita Indirli, Emanuele Bosi, Lorenzo Piemonti, Alessandro Aiuti, Manuela Battaglia, Georgia Fousteri

Research output: Contribution to journalArticlepeer-review

Abstract

Autoantibodies (AAbs) are a hallmark of Type 1 diabetes (T1D). Alterations in the frequency and phenotype of follicular helper (Tfh) T cells have been previously documented in patients with type 1 diabetes (T1D), but the contribution of follicular regulatory T (Treg) cells, which are responsible for suppressing AAb development, is less clear. Here, we investigated the frequency and activation status of follicular (CXCR5+) and conventional (CXCR5) Treg cells in the blood of children with new-onset T1D, and children with risk for developing T1D (AAb-positive) and compared them to AAb-negative controls. Blood follicular and conventional Treg cells were higher in frequency in children with new onset T1D, but expressed reduced amounts of PD-1 as compared to AAb-negative children. Interestingly, the proportion of circulating FOXP3+ Tregs expressing PD-1 was also reduced in AAb-positive at-risk children as compared to AAb-negative controls, suggesting its potential use as a biomarker of disease progression. Follicular Treg cells were reduced in frequency in the spleens of prediabetic NOD mice as they became older and turned diabetic. Interestingly, PD-1 expression declined also on circulating follicular and conventional Treg cells in prediabetic NOD mice as they aged. Together, these findings show that the frequency of circulating follicular and conventional Treg cells and their levels of PD-1 change with disease progression in children at-risk for developing T1D and in NOD mice.

Original languageEnglish
Article number108319
JournalClinical Immunology
Volume211
DOIs
Publication statusPublished - Feb 2020

Keywords

  • AAb-negative
  • AAb-positive
  • Autoantibodies (AAb)
  • CXCL13
  • Follicular Treg cells
  • PD-1
  • Regulatory T cells (Treg)
  • Tfh cells
  • Type 1 diabetes (T1D)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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