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

M.C. Rocha, L.M. Santos, E. Bagatin, J.W. Cohen Tervaert, J.G.M.C. Damoiseaux, A.V. Lido, A.L. Longhini, C.O. Torello, M.L. Queiroz

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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.
Original languageEnglish
Pages (from-to)562-569
Number of pages8
JournalInternational Journal of Hygiene and Environmental Health
Volume215
Issue number6
DOIs
Publication statusPublished - Nov 2012

Keywords

  • T cells
  • Silica
  • CTLA-4
  • PD-1
  • Polymorphisms
  • Autoimmunity
  • SYSTEMIC-LUPUS-ERYTHEMATOSUS
  • RHEUMATOID-ARTHRITIS
  • WEGENERS-GRANULOMATOSIS
  • AUTOIMMUNE-DISEASE
  • REGULATORY POLYMORPHISM
  • MULTIPLE-SCLEROSIS
  • NEGATIVE REGULATOR
  • PDCD1 GENE
  • ASSOCIATION
  • SUSCEPTIBILITY

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