Genetic polymorphisms and surface expression of CTLA-4 and PD-1 on T cells of silica-exposed workers

Int J Hyg Environ Health. 2012 Nov;215(6):562-9. doi: 10.1016/j.ijheh.2011.10.010. Epub 2011 Dec 5.

Abstract

Exposure to silica dust has been examined as a possible risk factor for autoimmune diseases, including scleroderma, rheumatoid arthritis and systemic lupus erythematosus. Since CTLA-4 [CD152] and PD-1 [CD279] are important for the maintenance of peripheral tolerance by regulating T cell responsiveness, we evaluated the expression of these molecules on the surface of CD4 and CD8 T cells, as well as single nucleotide polymorphisms (SNP) in CTLA-4 and PDCD1 genes, of 70 silica-exposed workers and 30 non-exposed, age-, ethnically- and sex-matched controls. Expression of CTLA-4 was significantly (P<0.05) reduced in CD4 T cells of exposed individuals [median=0.1% and interquartile range, IQR 0.0-0.1% (exposed), median=0.20%, IQR 0.0-0.4% (control)]. Also the expression of PD-1 was significantly (P<0.0001) reduced in both CD4 [median=0.9%, IQR 0.4-2.3% (exposed), median=5.7%, IQR 1.4-13.3% (control)] and CD8 T cells [median=0.9%, IQR 0.3-1.9% (exposed), median=5.0%, IQR 3.4-8.9% (control)]. The study of polymorphisms demonstrated a lower frequency of the A allele in the analysis of the PD1.3 SNP in the exposed group, which might be associated with the lower expression of PD-1 on the surface of CD4 T cells. Our findings provide evidence for the association of silica exposure and the maintenance of self-tolerance, i.e., the susceptibility to autoimmune disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • CD4 Lymphocyte Count
  • CTLA-4 Antigen / genetics*
  • CTLA-4 Antigen / metabolism
  • Case-Control Studies
  • Female
  • Flow Cytometry
  • Humans
  • Male
  • Middle Aged
  • Occupational Exposure*
  • Polymorphism, Single Nucleotide
  • Programmed Cell Death 1 Receptor / genetics*
  • Programmed Cell Death 1 Receptor / metabolism
  • Silicon Dioxide / immunology*
  • T-Lymphocytes / metabolism*

Substances

  • CTLA-4 Antigen
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Silicon Dioxide