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

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 HIVuninfected 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-c 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.