Treatment of type 1 diabetes by regulatory T-cell infusion via regulating the expression of inflammatory cytokines

J Cell Biochem. 2019 Dec;120(12):19338-19344. doi: 10.1002/jcb.27875. Epub 2019 Sep 18.

Abstract

Objective: To explore the role and molecular mechanism of regulatory T (Treg) cells in type 1 diabetes (T1D).

Methods: Patients with T1D and the healthy volunteers were selected and a number of CD3+ , CD4+ , CD25+ , and CD127- T cells were determined. The rats were divided into the control, T1D model, and Treg infusion (T1D rats were infused with Treg) group. The number of CD4+ , CD8- , and CD25+ T cells in the three groups were determined by flow cytometry. Weight, blood glucose, serum insulin, peptide C, glucagon, and glucagon like peptide 1 in the three groups were also determined. The messenger RNA (mRNA) levels and contents of interleukin (IL)-10, IL-4, transforming growth factor (TGF)-β, IL-2, IL-17, and IFN-γ in patients with T1D, healthy volunteers, streptozotocin (STZ)-induced T1D rat model, the control rat, and Treg infusion rats were determined by reverse transcription polymerase chain reaction and the enzyme-linked immunosorbent assay, respectively.

Results: Treg content in patients with T1D was significantly decreased compared with the control volunteers. Treg content in rats was markedly decreased after injection with STZ to induce T1D rat model, while Treg infusion weakened the decrease. The change scope of weight and blood glucose in the model and Treg group was bigger than the control group, and the change in the infusion group was lighter than the model group. T1D decreased the expressions of IL-10, IL-4, TGF-β, and IL-2, while Treg infusion weakened the decrease. The expressions of IL-17 and IFN-γ in the T1D group was increased, while Treg infusion weakened the increase.

Conclusion: Autologous Treg infusion can strengthen the immunologic and islet function to treat T1D which may be via regulating the expression of inflammatory factors.

Keywords: inflammatory; islet function; regulatory T (Treg) cells; type 1 diabetes (T1D).

MeSH terms

  • Animals
  • Cells, Cultured
  • Cytokines / genetics*
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / therapy*
  • Enzyme-Linked Immunosorbent Assay
  • Interferon-gamma / genetics
  • Interleukin-10 / genetics
  • Interleukin-2 / genetics
  • Interleukin-4 / genetics
  • Male
  • RNA, Messenger / genetics
  • Rats
  • Real-Time Polymerase Chain Reaction
  • T-Lymphocytes, Regulatory
  • Transforming Growth Factor beta / genetics

Substances

  • Cytokines
  • Interleukin-2
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma