Prolonged therapy, drug toxicity, non-compliance, immune suppression and alarming emergence of drug resistance necessitate the search for therapeutic vaccine strategies for tuberculosis (TB). Such strategies ought to elicit not only IFN-γ, but poly-functional response including TNF-α, which is essential for protective granuloma formation. Here, we investigated the impact of PD-1 inhibition in facilitating protective poly-functional T cells (PFTs), bacillary clearance and disease resolution. We have observed PD-1 inhibition preferentially rescued the suppressed PFTs in active tuberculosis patients. In addition,poly-functional cytokine milieu favoured apoptosis of infected MDMs over necrosis with markedly reduced bacillary growth (This article is protected by copyright. All rights reserved.