title: Relatively low level of antigen-specific monocytes detected in blood from untreated tuberculosis patients using CD4+ T-cell receptor tetramers.
abstract: The in vivo kinetics of antigen-presenting cells (APCs) in patients with advanced and convalescent tuberculosis (TB) is not well characterized. In order to target Mycobacterium tuberculosis (MTB) peptides- and HLA-DR-holding monocytes and macrophages, 2 MTB peptide-specific CD4(+) T-cell receptor (TCR) tetramers eu and hu were successfully constructed. Peripheral blood (PBL) samples from inpatients with advanced pulmonary TB (PTB) were analyzed using flow cytometry, and the percentages of tetramer-bound CD14(+) monocytes ranged from 0.26-1.44% and 0.21-0.95%, respectively; significantly higher than those measured in PBL samples obtained from non-TB patients, healthy donors, and umbilical cords. These tetramers were also able to specifically detect macrophages in situ via immunofluorescent staining. The results of the continuous time-point tracking of the tetramer-positive rates in PBL samples from active PTB outpatients undergoing treatment show that the median percentages were at first low before treatment, increased to their highest levels during the first month, and then began to decrease during the second month until finally reaching and maintaining a relatively low level after 3-6 months. These results suggest that there is a relatively low level of MTB-specific monocytes in advanced and untreated patients. Further experiments show that MTB induces apoptosis in CD14(+) cells, and the percentage of apoptotic monocytes dramatically decreases after treatment. Therefore, the relatively low level of MTB-specific monocytes is probably related to the apoptosis or necrosis of APCs due to live bacteria and their growth. The bactericidal effects of anti-TB drugs, as well as other unknown factors, would induce a peak value during the first month of treatment, and a relatively low level would be subsequently reached and maintained until all of the involved factors reached equilibrium. These tetramers have diagnostic potential and can provide valuable insights into the mechanisms of antigen presentation and its relationship with TB infection and latent TB infection.
authors.affiliation: Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Huang
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Yimin
authors.initials: Y
authors.lastname: Fang
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Jianbo
authors.initials: J
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Gao
authors.forename: Lirong
authors.initials: L
authors.lastname: Huang
authors.forename: Fangfang
authors.initials: F
authors.lastname: Yang
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.forename: Shuxian
authors.initials: S
authors.lastname: Lin
authors.forename: Yanan
authors.initials: Y
authors.lastname: Yao
authors.forename: Liangliang
authors.initials: L
authors.lastname: Ren
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.forename: Xuanjing
authors.initials: X
authors.lastname: Du
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.forename: Rongshun
authors.initials: R
authors.lastname: Wu
authors.forename: Kouxing
authors.initials: K
authors.lastname: Zhang
authors.forename: Lifang
authors.initials: L
authors.lastname: Jiang
authors.forename: Xinbing
authors.initials: X
authors.lastname: Yu
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Lai
mesh_terms: D000995:Antitubercular Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D009000:Monocytes / Q000276:immunology* / Q000473:pathology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013997:Time Factors; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology
chemical_list: D000995:Antitubercular Agents; D011948:Receptors, Antigen, T-Cell