TRAIL in CD8+ T cells from patients with severe aplastic anemia

Int J Hematol. 2017 Oct;106(4):490-499. doi: 10.1007/s12185-017-2279-0. Epub 2017 Jun 19.

Abstract

Severe aplastic anemia (SAA) is an autoimmune disease caused mainly by activated T lymphocytes. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of TNF family, which can induce apoptosis and play a significant role in the pathogenesis of many autoimmune disorders. In this study, we sought to investigate the role of TRAIL in peripheral CD8+ T cells (CTLs) from SAA patients to clarify the autoimmune mechanisms of bone marrow failure in SAA. The expression of TRAIL and TRAIL-R2 in CTLs from SAA patients and normal controls were determined by flow cytometry, real-time PCR, and western blot. Expression of perforin and granzyme B and apoptosis in CTLs were evaluated by flow cytometry. The expression of TRAIL and TRAIL-R2 in SAA patients was significantly decreased compared with controls; however, there was no statistical difference in TRAIL mRNA expression between the two groups. TRAIL expression in CTLs was negatively correlated with the expression of perforin and granzyme B, and negatively correlated with CTLs apoptosis in SAA patients. The TRAIL pathway may be responsible for abnormal CTL activation in SAA patients. Further study of TRAIL and its receptors may elucidate the pathogenesis of SAA.

Keywords: CTL; Severe aplastic anemia; TRAIL.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anemia, Aplastic / blood*
  • Anemia, Aplastic / pathology
  • CD8-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / pathology
  • Child
  • Child, Preschool
  • Female
  • Gene Expression Regulation*
  • Granzymes / blood
  • Humans
  • Male
  • Middle Aged
  • Perforin / blood
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / blood
  • Severity of Illness Index
  • TNF-Related Apoptosis-Inducing Ligand / blood*

Substances

  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFRSF10B protein, human
  • TNFSF10 protein, human
  • Perforin
  • GZMB protein, human
  • Granzymes