title: Mycobacterium tuberculosis specific CD8(+) T cells rapidly decline with antituberculosis treatment.
abstract: BACKGROUND
  Biomarkers associated with response to therapy in tuberculosis could have broad clinical utility. We postulated that the frequency of Mycobacterium tuberculosis (Mtb) specific CD8(+) T cells, by virtue of detecting intracellular infection, could be a surrogate marker of response to therapy and would decrease during effective antituberculosis treatment.
  
  
  OBJECTIVE
  We sought to determine the relationship of Mtb specific CD4(+) T cells and CD8(+) T cells with duration of antituberculosis treatment.
  
  
  METHODS
  We performed a prospective cohort study, enrolling between June 2008 and August 2010, of HIV-uninfected Ugandan adults (n = 50) with acid-fast bacillus smear-positive, culture confirmed pulmonary TB at the onset of antituberculosis treatment and the Mtb specific CD4(+) and CD8(+) T cell responses to ESAT-6 and CFP-10 were measured by IFN-γ ELISPOT at enrollment, week 8 and 24.
  
  
  RESULTS
  There was a significant difference in the Mtb specific CD8(+) T response, but not the CD4(+) T cell response, over 24 weeks of antituberculosis treatment (p<0.0001), with an early difference observed at 8 weeks of therapy (p = 0.023). At 24 weeks, the estimated Mtb specific CD8(+) T cell response decreased by 58%. In contrast, there was no significant difference in the Mtb specific CD4(+) T cell during the treatment. The Mtb specific CD4(+) T cell response, but not the CD8(+) response, was negatively impacted by the body mass index.
  
  
  CONCLUSIONS
  Our data provide evidence that the Mtb specific CD8(+) T cell response declines with antituberculosis treatment and could be a surrogate marker of response to therapy. Additional research is needed to determine if the Mtb specific CD8(+) T cell response can detect early treatment failure, relapse, or to predict disease progression.
authors: Department of Medicine, Oregon Health and Science University, Portland, Oregon, United States of America.
authors: Melissa R
authors: MR
authors: Nyendak
authors: Byung
authors: B
authors: Park
authors: Megan D
authors: MD
authors: Null
authors: Joy
authors: J
authors: Baseke
authors: Gwendolyn
authors: G
authors: Swarbrick
authors: Harriet
authors: H
authors: Mayanja-Kizza
authors: Mary
authors: M
authors: Nsereko
authors: Denise F
authors: DF
authors: Johnson
authors: Phineas
authors: P
authors: Gitta
authors: Alphonse
authors: A
authors: Okwera
authors: Stefan
authors: S
authors: Goldberg
authors: Lorna
authors: L
authors: Bozeman
authors: John L
authors: JL
authors: Johnson
authors: W Henry
authors: WH
authors: Boom
authors: Deborah A
authors: DA
authors: Lewinsohn
authors: David M
authors: DM
authors: Lewinsohn
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015992:Body Mass Index; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D044342:Malnutrition / Q000150:complications; D015999:Multivariate Analysis; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000276:immunology*; D010835:Phytohemagglutinins / Q000276:immunology; D013045:Species Specificity; D014376:Tuberculosis / Q000188:drug therapy* / Q000276:immunology*
chemical_list: D000995:Antitubercular Agents; D010835:Phytohemagglutinins