Mycobacterium tuberculosis Specific CD8+ T Cells Rapidly Decline with Antituberculosis Treatment

Details

• Alternative Title:
  PLoS One
• Personal Author:
  Nyendak, Melissa R. ; Park, Byung ; Null, Megan D. ; Baseke, Joy ; Swarbrick, Gwendolyn ; Mayanja-Kizza, Harriet ; Nsereko, Mary ; Johnson, Denise F. ; Gitta, Phineas ; Okwera, Alphonse ; Goldberg, Stefan ; Bozeman, Lorna ; Johnson, John L. ; Boom, W. Henry ; Lewinsohn, Deborah A. ; Lewinsohn, David M.
• Corporate Authors:
  for the Tuberculosis Research Unit and the Tuberculosis Trials Consortium
• Description:
  Rationale
  
  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.
  
  Materials and 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.
  
  
• Subjects:
  Adult Antitubercular Agents Body Mass Index CD8-Positive T-Lymphocytes Cohort Studies Female Humans Male Malnutrition Multivariate Analysis Mycobacterium Tuberculosis Phytohemagglutinins Species Specificity Tuberculosis

  More +
• Source:
  PLoS One. 2013; 8(12).
• Document Type:
  Journal Article
• Funding:
  200-2009-3259/PHS HHS/United States ; HHSN266200400081C/PHS HHS/United States ; HHSN266200700022C/NO1-AI-70022/AI/NIAID NIH HHS/United States ; HHSN272200900053C/PHS HHS/United States ; KL2RR024141/RR/NCRR NIH HHS/United States
• Volume:
  8
• Issue:
  12
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:11703a3e529470de337712b0c28caa3446b370fbfea52bf372fb0d887bb6d3db
• Download URL:
  https://stacks.cdc.gov/view/cdc/21396/cdc_21396_DS1.pdf
• File Type:
  [PDF - 654.25 KB ]