Reduced Expression of PD-1 in Circulating CD4+ and CD8+ Tregs Is an Early Feature of RRMS

Int J Mol Sci. 2022 Mar 16;23(6):3185. doi: 10.3390/ijms23063185.

Abstract

Altered regulatory T cell (Treg) function could contribute to MS. The expression of activating and inhibitory receptors influences the activity of Tregs. Our aim was to investigate T cell phenotypes in relapsing-remitting MS (RRMS) patients at an early phase of the disease. We examined the influence of demographic parameters on the distribution of CD4+ and CD8+ T cell subclasses by generalized linear modeling. We also studied the expression of the following markers-CTLA-4, GITR, PD-1, FoxP3, Helios, CD28, CD62L, CD103-on T cell subsets from peripheral blood with a 14-color flow cytometry panel. We used an antibody array to define the profiles of 34 Th1/Th2/Th17 cytokines in the serum. Expression of PD-1 and GITR on CD4+ and CD8+ Tregs was decreased in RRMS patients. The proinflammatory factors IFN-γ, IL-17, IL-17F, TGFβ-1, TGFβ-3, IL-1SRII, IL-12 p40, sgp130, IL-6sR were significantly increased in RRMS patients. Therefore, a deficiency of PD-1 and GITR immune checkpoints on CD4+ and CD8+ Tregs is a feature of RRMS and might underlie impaired T cell control.

Keywords: T cells; cytokines; relapsing–remitting multiple sclerosis; suppressive markers.

MeSH terms

  • CD8-Positive T-Lymphocytes
  • Humans
  • Programmed Cell Death 1 Receptor / immunology*
  • Programmed Cell Death 1 Receptor / metabolism
  • T-Lymphocyte Subsets
  • T-Lymphocytes, Regulatory*
  • Transforming Growth Factor beta / metabolism

Substances

  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Transforming Growth Factor beta