RescuesMycobacterium tuberculosis–Specific Interferon γ–Producing T Cells From Apoptosis in Patients With Pulmonary Tuberculosis

Background. Overexpression of programmed death 1 (PD-1) receptor is thought to inhibit the effector T-cell response in human tuberculosis. However, the precise mechanism of such inhibition remains unclear. The present study addresses the role of PD-1 in dampening host T-cell function among patients with pulmonary tuberculosis. Methods. Expression of PD-1 and its ligands (PD-L1/L2) on T cells, B cells, and monocytes was evaluated by flow cytometry (FACS). In vitro stimulation of peripheral blood mononuclear cells in the presence of Mycobacteri-um tuberculosis antigens was performed with and without blocking PD-1, and intracellular cytokine production was measured by FACS. Results. We showed higher frequencies of T cells, monocytes, and B cells expressing PD-1 and its ligand(s) among patients with pulmonary tuberculosis. Infections with live M. tuberculosis upregulated PD-L1 expression on monocytes. In vitro PD-1 blocking rescued M. tuberculosis–specific interferon γ (IFN-γ)–producing T cells from undergoing apoptosis. The number of PD-1–expressing T cells decreased significantly during therapy and inversely correlated with IFN-γ–dominant T-cell response againstM. tuberculosis. Conclusions. Manipulation of PD-1 signaling may restore the host T-cell response and thus may have therapeu-tic potential. PD-1 also may serve as a biomarker to monitor host immunity among patients with tuberculosis during therapy and vaccine studies