title: Inhibiting the programmed death 1 pathway rescues Mycobacterium tuberculosis-specific interferon γ-producing T cells from apoptosis in patients with pulmonary tuberculosis.
abstract: 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 Mycobacterium 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 against M. tuberculosis.
  
  
  CONCLUSIONS
  Manipulation of PD-1 signaling may restore the host T-cell response and thus may have therapeutic potential. PD-1 also may serve as a biomarker to monitor host immunity among patients with tuberculosis during therapy and vaccine studies.
authors: Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India.
authors: Amar
authors: A
authors: Singh
authors: Anant
authors: A
authors: Mohan
authors: Aparajit B
authors: AB
authors: Dey
authors: Dipendra K
authors: DK
authors: Mitra
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D001402:B-Lymphocytes / Q000737:chemistry / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000032:analysis / Q000037:antagonists & inhibitors / Q000276:immunology*; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology*; D055815:Young Adult
chemical_list: D016207:Cytokines; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D007371:Interferon-gamma
keywords: APCs and apoptosis; T cells; Tuberculosis; programmed death-1