title: Ex-vivo characterization of regulatory T cells in pulmonary tuberculosis patients, latently infected persons, and healthy endemic controls.
abstract: Regulatory T cells (Treg) are an essential arm of adaptive immunity not only in tolerance and autoimmunity but also in infectious diseases. In Tuberculosis (TB), it has been suggested that the frequency of Tregs is higher in the blood of TB patients when compared to healthy controls with subsequent decline after treatment. However, with the discovery that FOXP3, the hallmark marker of Tregs, is not exclusive to Tregs and the lack of specific markers for Tregs, it has been a challenge to fully understand the role of Tregs in TB.
  
  
  
  We isolated PBMC from smear positive TB patients (TB, N = 13) before and after treatment, latent TB infected participants (LTBI, N = 8), and healthy endemic controls (EC, N = 9) and evaluated the frequency of different populations of Tregs and expression of FOXP3 by flowcytometry using six markers.
  
  
  
  The findings in this study showed that the association of Treg frequency with TB disease depends on the phenotypic markers used. While the frequency of CD4(+)CD25(+/hi) T cells was higher in TB patients compared to LTBI individuals, there was no difference in the frequency of CD4(+)CD25(+)FOXP3(+)CD127(lo) Treg among TB, LTBI, or EC. However, delineation of Tregs into active and naïve subsets revealed a significant increase in FOXP3 expression in active primed Tregs (CD4(+)CD25(+)FOXP3(+)CD127(lo)CD45RO(+)Ki-67(+)) of TB patients compared to LTBI and EC; and a significantly higher frequency of resting primed (CD45RO(+)Ki-67(-)) Treg in QuantiFERON negative EC compared to TB patients. After treatment completion, there was a significant decline in the frequency of active primed Treg, median (IQR) from 12.4% (9.5-21.9) of Tregs to 9.3% (7.0-12.2); P = 0.003 Wilcoxon signed rank test. We conclude that Treg subsets may be differentially regulated and expressed in TB disease, cure, and infection.
authors.affiliation: Armauer Hansen Research Institute (AHRI), P.O. Box 1005, Jimma Road, Addis Ababa, Ethiopia. Electronic address: martha_zg@yahoo.co.uk.
authors.forename: Martha
authors.initials: M
authors.lastname: Zewdie
authors.affiliation: Armauer Hansen Research Institute (AHRI), P.O. Box 1005, Jimma Road, Addis Ababa, Ethiopia.
authors.forename: Rawleigh
authors.initials: R
authors.lastname: Howe
authors.affiliation: Department of Infectious Disease Immunology, Statens Serum Institut, Artillerivej 5, Copenhagen, Denmark.
authors.forename: Søren T
authors.initials: ST
authors.lastname: Hoff
authors.affiliation: Department of Infectious Disease Immunology, Statens Serum Institut, Artillerivej 5, Copenhagen, Denmark.
authors.forename: T Mark
authors.initials: TM
authors.lastname: Doherty
authors.affiliation: Armauer Hansen Research Institute (AHRI), P.O. Box 1005, Jimma Road, Addis Ababa, Ethiopia.
authors.forename: Nahom
authors.initials: N
authors.lastname: Getachew
authors.affiliation: Armauer Hansen Research Institute (AHRI), P.O. Box 1005, Jimma Road, Addis Ababa, Ethiopia.
authors.forename: Azeb
authors.initials: A
authors.lastname: Tarekegne
authors.affiliation: Armauer Hansen Research Institute (AHRI), P.O. Box 1005, Jimma Road, Addis Ababa, Ethiopia.
authors.forename: Bamlak
authors.initials: B
authors.lastname: Tessema
authors.affiliation: Armauer Hansen Research Institute (AHRI), P.O. Box 1005, Jimma Road, Addis Ababa, Ethiopia.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Yamuah
authors.affiliation: Armauer Hansen Research Institute (AHRI), P.O. Box 1005, Jimma Road, Addis Ababa, Ethiopia.
authors.forename: Abraham
authors.initials: A
authors.lastname: Aseffa
authors.affiliation: Armauer Hansen Research Institute (AHRI), P.O. Box 1005, Jimma Road, Addis Ababa, Ethiopia.
authors.forename: Markos
authors.initials: M
authors.lastname: Abebe
mesh_terms: D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000097:blood; D006801:Humans; D016130:Immunophenotyping; D055985:Latent Tuberculosis / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000276:immunology*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
keywords: FOXP3; Regulatory T cells; Tuberculosis