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We hypothesized that microbiological outcome was associated with stage-specific immune changes in peripheral whole blood during TB treatment. The T-cell phenotypes of treated TB patients were prospectively characterized in a blinded fashion using mass cytometry after <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (<jats:italic>Mtb<\/jats:italic>) antigen stimulation with QuantiFERON-TB Gold Plus, and then correlated to sputum culture status. At two months of treatment, cytotoxic and terminally differentiated CD8<jats:sup>+<\/jats:sup> T-cells were under-represented and na\u00efve CD4<jats:sup>+<\/jats:sup> T-cells were over-represented in positive- <jats:italic>versus<\/jats:italic> negative-sputum culture patients, regardless of <jats:italic>Mtb<\/jats:italic> drug susceptibility. At treatment completion, a T-cell immune shift towards differentiated subpopulations was associated with TB cure. 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