title: Genetic polymorphisms and surface expression of CTLA-4 and PD-1 on T cells of silica-exposed workers.
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.
authors.affiliation: Department of Pharmacology and Hemocenter, Faculty of Medical Sciences, FCM, State University of Campinas - UNICAMP, Campinas, SP, Brazil. microcha123@yahoo.com.br
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Rocha
authors.forename: Leonilda M B
authors.initials: LM
authors.lastname: Santos
authors.forename: Ericson
authors.initials: E
authors.lastname: Bagatin
authors.forename: Jan W
authors.initials: JW
authors.lastname: Cohen Tervaert
authors.forename: Jan G M C
authors.initials: JG
authors.lastname: Damoiseaux
authors.forename: Alessandro V
authors.initials: AV
authors.lastname: Lido
authors.forename: Ana L
authors.initials: AL
authors.lastname: Longhini
authors.forename: Cristiane O
authors.initials: CO
authors.lastname: Torello
authors.forename: Mary L S
authors.initials: ML
authors.lastname: Queiroz
mesh_terms: D000368:Aged; D018791:CD4 Lymphocyte Count; D060908:CTLA-4 Antigen / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D020641:Polymorphism, Single Nucleotide; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics* / Q000378:metabolism; D012822:Silicon Dioxide / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D060908:CTLA-4 Antigen; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D012822:Silicon Dioxide