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Relatively Low Level of Antigen-specific Monocytes Detected in Blood from Untreated Tuberculosis Patients Using CD4(+) T-cell Receptor Tetramers
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 (T...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3510242/ https://www.ncbi.nlm.nih.gov/pubmed/23209409 http://dx.doi.org/10.1371/journal.ppat.1003036 |
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author | Huang, Yuhong Huang, Yan Fang, Yimin Wang, Juan Li, Yan Wang, Nan Zhang, Jianbo Gao, Ming Huang, Lirong Yang, Fangfang Wang, Cong Lin, Shuxian Yao, Yanan Ren, Liangliang Chen, Yi Du, Xuanjing Xie, Dan Wu, Rongshun Zhang, Kouxing Jiang, Lifang Yu, Xinbing Lai, Xiaomin |
author_facet | Huang, Yuhong Huang, Yan Fang, Yimin Wang, Juan Li, Yan Wang, Nan Zhang, Jianbo Gao, Ming Huang, Lirong Yang, Fangfang Wang, Cong Lin, Shuxian Yao, Yanan Ren, Liangliang Chen, Yi Du, Xuanjing Xie, Dan Wu, Rongshun Zhang, Kouxing Jiang, Lifang Yu, Xinbing Lai, Xiaomin |
author_sort | Huang, Yuhong |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3510242 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35102422012-12-03 Relatively Low Level of Antigen-specific Monocytes Detected in Blood from Untreated Tuberculosis Patients Using CD4(+) T-cell Receptor Tetramers Huang, Yuhong Huang, Yan Fang, Yimin Wang, Juan Li, Yan Wang, Nan Zhang, Jianbo Gao, Ming Huang, Lirong Yang, Fangfang Wang, Cong Lin, Shuxian Yao, Yanan Ren, Liangliang Chen, Yi Du, Xuanjing Xie, Dan Wu, Rongshun Zhang, Kouxing Jiang, Lifang Yu, Xinbing Lai, Xiaomin PLoS Pathog Research Article 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. Public Library of Science 2012-11-29 /pmc/articles/PMC3510242/ /pubmed/23209409 http://dx.doi.org/10.1371/journal.ppat.1003036 Text en © 2012 Huang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Huang, Yuhong Huang, Yan Fang, Yimin Wang, Juan Li, Yan Wang, Nan Zhang, Jianbo Gao, Ming Huang, Lirong Yang, Fangfang Wang, Cong Lin, Shuxian Yao, Yanan Ren, Liangliang Chen, Yi Du, Xuanjing Xie, Dan Wu, Rongshun Zhang, Kouxing Jiang, Lifang Yu, Xinbing Lai, Xiaomin Relatively Low Level of Antigen-specific Monocytes Detected in Blood from Untreated Tuberculosis Patients Using CD4(+) T-cell Receptor Tetramers |
title | Relatively Low Level of Antigen-specific Monocytes Detected in Blood from Untreated Tuberculosis Patients Using CD4(+) T-cell Receptor Tetramers |
title_full | Relatively Low Level of Antigen-specific Monocytes Detected in Blood from Untreated Tuberculosis Patients Using CD4(+) T-cell Receptor Tetramers |
title_fullStr | Relatively Low Level of Antigen-specific Monocytes Detected in Blood from Untreated Tuberculosis Patients Using CD4(+) T-cell Receptor Tetramers |
title_full_unstemmed | Relatively Low Level of Antigen-specific Monocytes Detected in Blood from Untreated Tuberculosis Patients Using CD4(+) T-cell Receptor Tetramers |
title_short | Relatively Low Level of Antigen-specific Monocytes Detected in Blood from Untreated Tuberculosis Patients Using CD4(+) T-cell Receptor Tetramers |
title_sort | relatively low level of antigen-specific monocytes detected in blood from untreated tuberculosis patients using cd4(+) t-cell receptor tetramers |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3510242/ https://www.ncbi.nlm.nih.gov/pubmed/23209409 http://dx.doi.org/10.1371/journal.ppat.1003036 |
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