Improved Mycobacterium tuberculosis clearance after restoration of IFN-γ+ TNF-α+ CD4+ T cells: Impact of PD-1 inhibition in active tuberculosis patients.

Prolonged therapy, drug toxicity, noncompliance, 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-gamma, but polyfunctional response including TNF-alpha, which is essential for protective granuloma formation. Here, we investigated the impact of PD-1 inhibition in facilitating protective polyfunctional 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, polyfunctional cytokine milieu favored apoptosis of infected MDMs over necrosis with markedly reduced bacillary growth (<

Keywords:

• Immunotherapy
• Immunology
• Mycobacterium tuberculosis
• Biology
• Tumor necrosis factor alpha
• Tuberculosis
• Spleen
• Necrosis
• Drug resistance
• Immune system
• In vivo

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