title: The characteristic profiles of PD-1 and PD-L1 expressions and dynamic changes during treatment in active tuberculosis.
abstract: 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.
authors.affiliation: Department of Thoracic Intensive Care Unit and Anesthesiology, Shanghai Pulmonary Hospital, Shanghai, 200433, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Thoracic Intensive Care Unit and Anesthesiology, Shanghai Pulmonary Hospital, Shanghai, 200433, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Pulmonary Diseases, Wuxi Infectious Diseases Hospital, Wuxi, 214005, China.
authors.forename: Qinfang
authors.initials: Q
authors.lastname: Ou
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China; Key Laboratory of Medical Molecular Virology, Ministry of Education and Health, Shanghai Medical College, and Institutes of Biomedical Science, Fudan University, Shanghai, 200032, China.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Clinic and Research Center of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, 200433, China. Electronic address: fanlinsj@163.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China. Electronic address: lingyun26@fudan.edu.cn.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Shao
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D006801:Humans; D061026:Programmed Cell Death 1 Receptor / Q000097:blood*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016896:Treatment Outcome; D014376:Tuberculosis / Q000188:drug therapy / Q000276:immunology*
chemical_list: D000995:Antitubercular Agents; D060890:B7-H1 Antigen; D015415:Biomarkers; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: PD-1; PD-L1; T cell subsets; Tuberculosis