Absolute reduction of regulatory T cells and regulatory effect of short-term and low-dose IL-2 in polymyositis or dermatomyositis

Int Immunopharmacol. 2019 Dec:77:105912. doi: 10.1016/j.intimp.2019.105912. Epub 2019 Oct 24.

Abstract

Aim: The study aimed to investigate the changes in peripherallymphocyte and CD4+T subsets and to observe the regulatory effect of low-dose interleukin-2 (ld-IL2) on these cells in polymyositis or dermatomyositis (PM/DM).

Methods: Lymphocyte subsets (CD3+T, CD4+T, CD8+T, B and natural killer (NK) cells), CD4+T subsets (Th1, Th2, Th17 and regulatory T (Treg) cells) and multiple cytokines of 71 patients after admission and treatment were measured by flow cytometry, as well as these indicators in 30 healthy controls (HCs). In DM, 35 cases were administrated with ld-IL2 combined with conventional therapy, the remaining 26 patients received conventional therapy only.

Results: The numbers of CD3+T and CD4+T cells in PM/DM were markedly decreased. Meanwhile, the absolute number and percentage of peripheral Treg cells in PM/DM, as well as Th1 cells in DM, were significantly lower than those in HCs (P < 0.05), but Th2 and Th17 cells had no significant difference. The ratio of Th17/Treg in PM (P = 0.031) and in DM (P = 0.003) were obviously higher than that in HCs. The deficiency of Treg cells was associated with the occurrence of interstitial lung disease (ILD) in myositis patients. Meanwhile, reduced production of IL-2 was also observed in PM/DM (P < 0.001). ld-IL2 combination therapy could significantly increase the numbers of CD4+T subsets in DM, especially Treg cells (expanded 2.5 times).

Conclusions: The decline of peripheral Treg cells and serum IL-2 were found in PM/DM. ld-IL2 combination therapy could significantly increase the number of Treg cells.

Keywords: Dermatomyositis; Immune tolerance; Interleukin-2; Polymyositis; Regulatory T cells.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Cytokines / blood*
  • Dermatomyositis / blood
  • Dermatomyositis / immunology*
  • Female
  • Humans
  • Interleukin-2 / pharmacology*
  • Male
  • Middle Aged
  • Polymyositis / blood
  • Polymyositis / immunology*
  • Recombinant Proteins / pharmacology
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology

Substances

  • Cytokines
  • IL2 protein, human
  • Interleukin-2
  • Recombinant Proteins