Mycobacterium tuberculosis specific CD8+ T cells rapidly decline with antituberculosis treatment

Melissa R. Nyendak, Byung Park, Megan D. Null, Joy Baseke, Gwendolyn Swarbrick, Harriet Mayanja-Kizza, Mary Nsereko, Denise F. Johnson, Phineas Gitta, Alphonse Okwera, Stefan Goldberg, Lorna Bozeman, John L. Johnson, W. Henry Boom, Deborah A. Lewinsohn, David M. Lewinsohn

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

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. Objectives: We sought to determine the relationship of Mtb specific CD4 + T cells and CD8+ T cells with duration of 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.

Original languageEnglish (US)
Article numbere81564
JournalPloS one
Volume8
Issue number12
DOIs
StatePublished - Dec 4 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Nyendak, M. R., Park, B., Null, M. D., Baseke, J., Swarbrick, G., Mayanja-Kizza, H., Nsereko, M., Johnson, D. F., Gitta, P., Okwera, A., Goldberg, S., Bozeman, L., Johnson, J. L., Boom, W. H., Lewinsohn, D. A., & Lewinsohn, D. M. (2013). Mycobacterium tuberculosis specific CD8+ T cells rapidly decline with antituberculosis treatment. PloS one, 8(12), [e81564]. https://doi.org/10.1371/journal.pone.0081564