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

Melissa 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 Lewinsohn, David Lewinsohn

Research output: Contribution to journalArticle

27 Citations (Scopus)

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+ 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

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T-cells
Mycobacterium tuberculosis
T-lymphocytes
T-Lymphocytes
Therapeutics
Biomarkers
therapeutics
Enzyme-Linked Immunospot Assay
relapse
Bacilli
Treatment Failure
cohort studies
disease course
tuberculosis
Bacillus
body mass index
Disease Progression
biomarkers
Tuberculosis
Body Mass Index

ASJC Scopus subject areas

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

Cite this

Mycobacterium tuberculosis specific CD8+ T cells rapidly decline with antituberculosis treatment. / Nyendak, Melissa; 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; Lewinsohn, David.

In: PLoS One, Vol. 8, No. 12, e81564, 04.12.2013.

Research output: Contribution to journalArticle

Nyendak, M, Park, B, Null, MD, Baseke, J, Swarbrick, G, Mayanja-Kizza, H, Nsereko, M, Johnson, DF, Gitta, P, Okwera, A, Goldberg, S, Bozeman, L, Johnson, JL, Boom, WH, Lewinsohn, D & Lewinsohn, D 2013, 'Mycobacterium tuberculosis specific CD8+ T cells rapidly decline with antituberculosis treatment', PLoS One, vol. 8, no. 12, e81564. https://doi.org/10.1371/journal.pone.0081564
Nyendak, Melissa ; 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 ; Lewinsohn, David. / Mycobacterium tuberculosis specific CD8+ T cells rapidly decline with antituberculosis treatment. In: PLoS One. 2013 ; Vol. 8, No. 12.
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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+ 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.",
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