期刊
JOURNAL OF INFECTIOUS DISEASES
卷 208, 期 4, 页码 603-615出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jit206
关键词
Tuberculosis; programmed death-1; T cells; APCs and apoptosis
资金
- Department of Biotechnology
- Indian Council of Medical Research, New Delhi, India
- All India Institute of Medical Sciences
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 gamma (IFN-gamma)-producing T cells from undergoing apoptosis. The number of PD-1-expressing T cells decreased significantly during therapy and inversely correlated with IFN-gamma-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.
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