Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
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
_version_ 1782251441311711232
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
work_keys_str_mv AT huangyuhong relativelylowlevelofantigenspecificmonocytesdetectedinbloodfromuntreatedtuberculosispatientsusingcd4tcellreceptortetramers
AT huangyan relativelylowlevelofantigenspecificmonocytesdetectedinbloodfromuntreatedtuberculosispatientsusingcd4tcellreceptortetramers
AT fangyimin relativelylowlevelofantigenspecificmonocytesdetectedinbloodfromuntreatedtuberculosispatientsusingcd4tcellreceptortetramers
AT wangjuan relativelylowlevelofantigenspecificmonocytesdetectedinbloodfromuntreatedtuberculosispatientsusingcd4tcellreceptortetramers
AT liyan relativelylowlevelofantigenspecificmonocytesdetectedinbloodfromuntreatedtuberculosispatientsusingcd4tcellreceptortetramers
AT wangnan relativelylowlevelofantigenspecificmonocytesdetectedinbloodfromuntreatedtuberculosispatientsusingcd4tcellreceptortetramers
AT zhangjianbo relativelylowlevelofantigenspecificmonocytesdetectedinbloodfromuntreatedtuberculosispatientsusingcd4tcellreceptortetramers
AT gaoming relativelylowlevelofantigenspecificmonocytesdetectedinbloodfromuntreatedtuberculosispatientsusingcd4tcellreceptortetramers
AT huanglirong relativelylowlevelofantigenspecificmonocytesdetectedinbloodfromuntreatedtuberculosispatientsusingcd4tcellreceptortetramers
AT yangfangfang relativelylowlevelofantigenspecificmonocytesdetectedinbloodfromuntreatedtuberculosispatientsusingcd4tcellreceptortetramers
AT wangcong relativelylowlevelofantigenspecificmonocytesdetectedinbloodfromuntreatedtuberculosispatientsusingcd4tcellreceptortetramers
AT linshuxian relativelylowlevelofantigenspecificmonocytesdetectedinbloodfromuntreatedtuberculosispatientsusingcd4tcellreceptortetramers
AT yaoyanan relativelylowlevelofantigenspecificmonocytesdetectedinbloodfromuntreatedtuberculosispatientsusingcd4tcellreceptortetramers
AT renliangliang relativelylowlevelofantigenspecificmonocytesdetectedinbloodfromuntreatedtuberculosispatientsusingcd4tcellreceptortetramers
AT chenyi relativelylowlevelofantigenspecificmonocytesdetectedinbloodfromuntreatedtuberculosispatientsusingcd4tcellreceptortetramers
AT duxuanjing relativelylowlevelofantigenspecificmonocytesdetectedinbloodfromuntreatedtuberculosispatientsusingcd4tcellreceptortetramers
AT xiedan relativelylowlevelofantigenspecificmonocytesdetectedinbloodfromuntreatedtuberculosispatientsusingcd4tcellreceptortetramers
AT wurongshun relativelylowlevelofantigenspecificmonocytesdetectedinbloodfromuntreatedtuberculosispatientsusingcd4tcellreceptortetramers
AT zhangkouxing relativelylowlevelofantigenspecificmonocytesdetectedinbloodfromuntreatedtuberculosispatientsusingcd4tcellreceptortetramers
AT jianglifang relativelylowlevelofantigenspecificmonocytesdetectedinbloodfromuntreatedtuberculosispatientsusingcd4tcellreceptortetramers
AT yuxinbing relativelylowlevelofantigenspecificmonocytesdetectedinbloodfromuntreatedtuberculosispatientsusingcd4tcellreceptortetramers
AT laixiaomin relativelylowlevelofantigenspecificmonocytesdetectedinbloodfromuntreatedtuberculosispatientsusingcd4tcellreceptortetramers