Function of T regulatory type 1 cells is down-regulated and is associated with the clinical presentation of coronary artery disease

Hum Immunol. 2018 Jul;79(7):564-570. doi: 10.1016/j.humimm.2018.05.001. Epub 2018 May 3.

Abstract

T regulatory type 1 (Tr1) cells can promote tolerance and suppress inflammation. Atherosclerosis may be induced by the proinflammatory activation of cells in the vasculature and the immune system. Hence, we wondered whether defects in Tr1 function were a contributing factor to coronary artery disease (CAD). Data showed that the frequency of IL-10+ Tr1 cells was significantly lower in CAD patients than in controls. Compared to healthy controls, Tr1 cells from CAD patients presented lower CTLA-4 but higher PD-1 expression, in addition to lower IL-10 secretion. When co-incubated with Tconv cells, the CD4+CD49b+LAG-3+CD45RO+ Tr1 cells presented IL-10-dependent inhibitory effects, and those from CAD patients presented significantly lower suppression capacity than those from healthy controls. Interestingly, the characteristics of Tr1 cells were associated with clinical features of CAD patients. The frequency of Tr1 cells and the IL-10 and LAG-3 expression by Tr1 cells were negatively correlated with the BMI of the CAD patients. In addition, the Tr1 frequency and the LAG-3 and CTLA-4 expression on Tr1 cells were lower in CAD patients with higher numbers of narrowed vessels. Together, these results suggest that in CAD, Tr1 cells present multiple defects, which are associated with the clinical presentation of the disease.

Keywords: Coronary artery disease; IL-10; Tr1 cell.

MeSH terms

  • Aged
  • Antigens, CD / metabolism
  • CTLA-4 Antigen / metabolism
  • Cells, Cultured
  • Coculture Techniques
  • Coronary Artery Disease / immunology*
  • Female
  • Humans
  • Immune Tolerance
  • Interleukin-10 / metabolism
  • Lymphocyte Activation Gene 3 Protein
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • Th1 Cells / immunology*

Substances

  • Antigens, CD
  • CTLA-4 Antigen
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Interleukin-10
  • Lymphocyte Activation Gene 3 Protein
  • Lag3 protein, human