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

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.