title: Resting and Activated Natural Tregs Decrease in the Peripheral Blood of Patients with Atherosclerosis.
abstract: BACKGROUND
  Atherosclerosis is a chronic inflammatory disease affecting large and medium arteries. CD4+ T cells are known to play a role in the progression of the disease. CD4+CD25+Foxp3+ natural Treg (nTreg) cells seem to have a protective role in the disease and their reduction in acute coronary syndrome is recently shown.
  
  
  OBJECTIVE
  To investigate the frequency of nTreg subsets in the peripheral blood of patients with atherosclerosis.
  
  
  METHODS
  Confirmation of atherosclerosis was done by angiography and 15 ml heparinized blood was obtained from each of the 13 non-diabetic patients and 13 non-diabetic, non-smoker individuals with normal/insignificant coronary artery disease confirmed by angiography. Lipid profiles of the patients and controls were measured at the time of sampling. Mononuclear cells were used for both RNA extraction and immunophenotyping by real-time PCR and flowcytometry techniques, respectively.
  
  
  RESULTS
  In natural Treg subsets, the frequency of CD4+CD45RO-CD25+Foxp3lo T-cells (resting nTregs) was greater in controls than patients (p=0.02). The frequency of CD4+CD45RO+CD25hiFoxp3hi T-cells (activated nTregs) was significantly higher in controls compared with patients (p=0.02). However, the frequency of CD4+CD25+CD45RO+Foxp3- T-cells (effector/memory T-cell) increased in patients compared with controls (p=0.01). Both the MFI and gene expression of Foxp3 were higher in control group than in patients (p=0.015 and p=0.017, respectively). Moreover, the TGF-β gene expression showed a decrease in the peripheral blood mononuclear cells of patients compared with controls (p=0.03).
  
  
  CONCLUSIONS
  Decrease in both subsets of resting and activated nTregs along with a decrease in the expression of Foxp3 and TGF-β genes in patients with atherosclerosis suggests phenotypic changes in these subsets, which may as well be correlated with a more inflammatory profile in their lymphocytes.
authors.affiliation: Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Yazdani
authors.forename: Shahdad
authors.initials: S
authors.lastname: Khosropanah
authors.forename: Ahmad
authors.initials: A
authors.lastname: Hosseini
authors.forename: Mehrnoosh
authors.initials: M
authors.lastname: Doroudchi
mesh_terms: D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000097:blood* / Q000175:diagnosis / Q000276:immunology*; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D008055:Lipids / Q000097:blood; D008213:Lymphocyte Activation / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D008055:Lipids; D016212:Transforming Growth Factor beta