title: CD137 is a Useful Marker for Identifying CD4+T Cell Responses to Mycobacterium tuberculosis.
abstract: Upregulation of CD137 on recently activated CD8+T cells has been used to identify rare viral and tumour antigen-specific T cells from the peripheral blood. We aimed to evaluate the accuracy of CD137 for identifying Mycobacterium tuberculosis (Mtb)-reactive CD4+T cells in the peripheral blood of infected individuals by flow cytometry and to investigate the characteristics of these CD137+CD4+T cells. We initially enrolled 31 active tuberculosis (TB) patients, 31 individuals with latent TB infection (LTBI) and 25 healthy donors. The intracellular CD137 and interferon-γ (IFN-γ) production by CD4+T cells was simultaneously detected under unstimulated and CFP10-stimulated (culture filtrate protein 10, a Mtb-specific antigen) conditions. In unstimulated CD4+T cells, we found that the CD137 expression in the TB group was significantly higher than that in the LTBI group. Stimulation with CFP10 largely increased the CD4+T cell CD137 expression in both the TB and LTBI groups. After CFP10 stimulation, the frequency of CD137+CD4+T cells was higher than that of IFN-γ+CD4+T cells in both the TB and LTBI groups. Most of the CFP10-activated IFN-γ-secreting cells were CD137-positive, but only a small fraction of the CD137-positive cells expressed IFN-γ. An additional 20 patients with TB were enrolled to characterize the CD45RO+CCR7+, CD45RO+CCR7-and CD45RO-subsets in the CD137+CD4+T cell populations. The Mtb-specific CD137+CD4+T cells were mainly identified as having an effector memory phenotype. In conclusion, CD137 is a useful marker that can be used for identifying Mtb-reactive CD4+T cells by flow cytometry.
authors.affiliation: Department of Central Laboratory, Beijing Key Laboratory for Drug Resistance Tuberculosis Research, Beijing Chest Hospital, Capital Medical University and, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
authors.forename: Z-H
authors.initials: ZH
authors.lastname: Yan
authors.affiliation: Department of Pathology, Capital Medical University, Beijing Chao-yang Hospital, Beijing, China.
authors.forename: X-F
authors.initials: XF
authors.lastname: Zheng
authors.affiliation: Department of Central Laboratory, Beijing Key Laboratory for Drug Resistance Tuberculosis Research, Beijing Chest Hospital, Capital Medical University and, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Yi
authors.affiliation: Department of Central Laboratory, Beijing Key Laboratory for Drug Resistance Tuberculosis Research, Beijing Chest Hospital, Capital Medical University and, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Central Laboratory, Beijing Key Laboratory for Drug Resistance Tuberculosis Research, Beijing Chest Hospital, Capital Medical University and, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
authors.forename: X-J
authors.initials: XJ
authors.lastname: Wang
authors.affiliation: Department of Central Laboratory, Beijing Key Laboratory for Drug Resistance Tuberculosis Research, Beijing Chest Hospital, Capital Medical University and, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
authors.forename: P-J
authors.initials: PJ
authors.lastname: Wei
authors.affiliation: Department of Central Laboratory, Beijing Key Laboratory for Drug Resistance Tuberculosis Research, Beijing Chest Hospital, Capital Medical University and, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
authors.forename: H-Y
authors.initials: HY
authors.lastname: Jia
authors.affiliation: Department of Central Laboratory, Navy General Hospital, Beijing, China.
authors.forename: L-J
authors.initials: LJ
authors.lastname: Zhou
authors.affiliation: Department of National Tuberculosis Reference Laboratory, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Y-L
authors.initials: YL
authors.lastname: Zhao
authors.affiliation: Department of Central Laboratory, Beijing Key Laboratory for Drug Resistance Tuberculosis Research, Beijing Chest Hospital, Capital Medical University and, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
authors.forename: H-T
authors.initials: HT
authors.lastname: Zhang
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D005260:Female; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D055985:Latent Tuberculosis / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000502:physiology; D014376:Tuberculosis / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000276:immunology* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D007371:Interferon-gamma