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

MR Nyendak, B Park, MD Null, J Baseke, G Swarbrick… - Plos one, 2013 - journals.plos.org
MR Nyendak, B Park, MD Null, J Baseke, G Swarbrick, H Mayanja-Kizza, M Nsereko…
Plos one, 2013journals.plos.org
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 …
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.
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