title: Evaluation of CD4+ CD25+ FoxP3+ Regulatory T cells and FoxP3 and CTLA-4 gene Expression in Patients wwith Newly Diagnosed Tuberculosis in Northeast of Iran.
abstract: BACKGROUND
  Tuberculosis (TB) is the world's second most common infectious disease after Human Immunodeficiency Virus Infection/Acquired Immunodeficiency Syndrome (HIV/AID) and the most frequent cause of mortality especially in developing countries. T regulatory (Treg) cells, which have suppressive activity and express forkhead winged-helix family transcriptional repressor p3 (FoxP3), suppress the immune responses against pathogens such as Mycobacterium tuberculosis. There are controversial results regarding the role of FoxP3 expressing cells in the blood of patients with TB.
  
  
  OBJECTIVE
  The aim of this study was to evaluate the frequency CD4+ CD25+ Treg cells, and FoxP3 and Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) gene expressions in peripheral blood of patients with tuberculosis and patients with positive tuberculin skin test before and after Peripheral Blood Mononuclear Cells (PBMCs) activation with Purified Protein Derivative (PPD).
  
  
  METHODS
  In this cross-sectional study, Peripheral Mononuclear Cells (PBMCs) were isolated from peripheral blood of 29 patients with newly diagnosed pulmonary TB and 19 patients with positive tuberculin skin test. The PBMCs were activated with PPD for 72 hours. Activated cells were harvested, RNA was extracted and cDNA was synthesized. A real-time Taqman method was designed and optimized for evaluation of Foxp3 gene expression and SYBR Green method was used and optimized for evaluation of CTLA-4 gene expression. A flow cytometry analysis was used to evaluate the frequency of CD4+ CD25+ Foxp3+ regulatory T cells in both groups.
  
  
  RESULTS
  There was no significant difference in the frequency of CD4+ CD25+ FoxP3+ regulatory T cells between the two groups. Expression of FoxP3 and CTLA-4 in peripheral blood of patients with newly diagnosed TB was significantly lower than the control group after and before activation with PPD.
  
  
  CONCLUSIONS
  The expression of FoxP3 and CTLA-4 in PBMCs of patients with newly diagnosed TB was low, which might suggest that Treg cells may be sequestered in the lungs.
authors.affiliation: Inflammation and Inflammatory Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, IR Iran.
authors.forename: Roghayeh
authors.initials: R
authors.lastname: Ghazalsofala
authors.affiliation: Inflammation and Inflammatory Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, IR Iran.
authors.forename: Seyed Abdolrahim
authors.initials: SA
authors.lastname: Rezaee
authors.affiliation: Rheumatic Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, IR Iran.
authors.forename: Houshang
authors.initials: H
authors.lastname: Rafatpanah
authors.affiliation: Inflammation and Inflammatory Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, IR Iran.
authors.forename: Rosita
authors.initials: R
authors.lastname: Vakili
authors.affiliation: Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, IR Iran.
authors.forename: Kiarash
authors.initials: K
authors.lastname: Ghazvini
authors.affiliation: Inflammation and Inflammatory Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, IR Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Heidarnejad
authors.affiliation: Inflammation and Inflammatory Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, IR Iran.
authors.forename: Somaye
authors.initials: S
authors.lastname: Sobhani
authors.affiliation: Inflammation and Inflammatory Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, IR Iran.
authors.forename: Narges
authors.initials: N
authors.lastname: Valizadeh
authors.affiliation: Chronic Obstructive Pulmonary Disease Research Center, Mashhad University of Medical Sciences, Mashhad, IR Iran.
authors.forename: Marayam
authors.initials: M
authors.lastname: Azami
authors.affiliation: Infection Diseases Department, Mashhad University of Medical Sciences, Mashhad, IR Iran.
authors.forename: Marzieh
authors.initials: M
authors.lastname: Rahimzadegan
authors.affiliation: Chronic Obstructive Pulmonary Disease Research Center, Mashhad University of Medical Sciences, Mashhad, IR Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Asnaashari
keywords: Cytotoxic T-lymphocyte associated antigen 4 (CTLA-4 Antigen); T-Lymphocytes, Regulatory; Tuberculosis