The characteristic profiles of PD-1 and PD-L1 expressions and dynamic changes during treatment in active tuberculosis

• Published in: Tuberculosis (Edinburgh, Scotland) Vol. 101; pp. 146 - 150
• Main Authors: Shen, Lei, Shi, Hong, Gao, Yan, Ou, Qinfang, Liu, Qianqian, Liu, Yuanyuan, Wu, Jing, Zhang, Wenhong, Fan, Lin, Shao, Lingyun
• Format: Journal Article
• Language: English
• Published: Scotland Elsevier Ltd 01.12.2016; Elsevier Science Ltd
• Subjects: Animal models; Antitubercular Agents - therapeutic use; B7-H1 Antigen - blood; Biomarkers - blood; Case-Control Studies; CD25 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; Cell surface; Cells; Drug resistance; Foxp3 protein; Gene expression; Humans; Immunology; Immunoregulation; Immunotherapy; Infectious Disease; Lymphocytes; Lymphocytes B; Lymphocytes T; Pathogenesis; Patients; PD-1; PD-1 protein; PD-L1; PD-L1 protein; Programmed Cell Death 1 Receptor - blood; Public health; Pulmonary/Respiratory; Subpopulations; T cell subsets; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Regulatory - immunology; Therapy; Treatment Outcome; Tuberculosis; Tuberculosis - drug therapy; Tuberculosis - immunology; PD-L1; Tuberculosis; T cell subsets; PD-1
• ISSN: 1472-9792; 1873-281X
• DOI: 10.1016/j.tube.2016.10.001

PD-1 is a cell surface receptor of activated T and B lymphocytes and it's role in tuberculosis is controversial because of lack of congruence between clinical study and animal model. To investigate the immunological pathogenesis mechanisms of tuberculosis and to develop the immune therapy target essential for controlling tuberculosis, here we explored the expression characteristics and dynamic changes of PD-1/PD-L1 pathway in different CD4+T cell subsets. We enrolled 24 human subjects including 15 active tuberculosis (ATB) patients and 9 healthy donors (HD). The expressions of PD-1 and PD-L1 on CD4+T cells increased significantly in ATB patients than HD. ATB patients had a higher proportion of regulatory T cells (Treg, CD4+CD25 + Foxp3+) than HD. The expressions of PD-1 and PD-L1 increased remarkably on CD4+T cell subsets, including Treg cells, Tresp (CD4+CD25−) cells and Teff (CD4+CD25 + Foxp3-) cells. Finally, clinical improvement following effective anti-TB therapy is correlated with significantly decreased expression of PD-1 in Tresp and Teff cells, but not in Treg cells. Thus, expression profiles of PD-1 in T cell subpopulations may be used as a candidate to predict the clinical efficacy of anti-tuberculosis therapy. Modulation of PD-1/PD-L1 pathway in CD4 subsets may offer an immunotherapy target for the control of tuberculosis.