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Production of Proinflammatory Cytokines by CD4+ and CD8+ T Cells in Response to Mycobacterial Antigens among Children and Adults with Tuberculosis.

作者信息

Morrow Erin, Liu Qijia, Kiguli Sarah, Swarbrick Gwendolyn, Nsereko Mary, Null Megan D, Cansler Meghan, Mayanja-Kizza Harriet, Boom W Henry, Chheng Phalkun, Nyendak Melissa R, Lewinsohn David M, Lewinsohn Deborah A, Lancioni Christina L

机构信息

School of Medicine, Oregon Health and Science University, Portland, OR 97239, USA.

School of Public Health, Oregon Health and Science University, Portland, OR 97239, USA.

出版信息

Pathogens. 2023 Nov 14;12(11):1353. doi: 10.3390/pathogens12111353.


DOI:10.3390/pathogens12111353
PMID:38003817
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10675744/
Abstract

Tuberculosis (TB), caused by (Mtb), remains a leading cause of pediatric morbidity and mortality. Young children are at high risk of TB following Mtb exposure, and this vulnerability is secondary to insufficient host immunity during early life. Our primary objective was to compare CD4+ and CD8+ T-cell production of proinflammatory cytokines IFN-gamma, IL-2, and TNF-alpha in response to six mycobacterial antigens and superantigen staphylococcal enterotoxin B (SEB) between Ugandan adults with confirmed TB (n = 41) and young Ugandan children with confirmed (n = 12) and unconfirmed TB (n = 41), as well as non-TB lower respiratory tract infection (n = 39). Flow cytometry was utilized to identify and quantify CD4+ and CD8+ T-cell cytokine production in response to each mycobacterial antigen and SEB. We found that the frequency of CD4+ and CD8+ T-cell production of cytokines in response to SEB was reduced in all pediatric cohorts when compared to adults. However, T-cell responses to Mtb-specific antigens ESAT6 and CFP10 were equivalent between children and adults with confirmed TB. In contrast, cytokine production in response to ESAT6 and CFP10 was limited in children with unconfirmed TB and absent in children with non-TB lower respiratory tract infection. Of the five additional mycobacterial antigens tested, PE3 and PPE15 were broadly recognized regardless of TB disease classification and age. Children with confirmed TB exhibited robust proinflammatory CD4+ and CD8+ T-cell responses to Mtb-specific antigens prior to the initiation of TB treatment. Our findings suggest that adaptive proinflammatory immune responses to Mtb, characterized by T-cell production of IFN-gamma, IL-2, and TNF-alpha, are not impaired during early life.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d1a/10675744/5faa53b177b0/pathogens-12-01353-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d1a/10675744/a8e9088302ca/pathogens-12-01353-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d1a/10675744/3ddba6e26a25/pathogens-12-01353-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d1a/10675744/22e203f6d0f7/pathogens-12-01353-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d1a/10675744/d5caf7d3da1e/pathogens-12-01353-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d1a/10675744/5faa53b177b0/pathogens-12-01353-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d1a/10675744/a8e9088302ca/pathogens-12-01353-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d1a/10675744/3ddba6e26a25/pathogens-12-01353-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d1a/10675744/22e203f6d0f7/pathogens-12-01353-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d1a/10675744/d5caf7d3da1e/pathogens-12-01353-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d1a/10675744/5faa53b177b0/pathogens-12-01353-g005.jpg

相似文献

[1]
Production of Proinflammatory Cytokines by CD4+ and CD8+ T Cells in Response to Mycobacterial Antigens among Children and Adults with Tuberculosis.

Pathogens. 2023-11-14

[2]
Functional Signatures of Human CD4 and CD8 T Cell Responses to Mycobacterium tuberculosis.

Front Immunol. 2014-4-22

[3]
Cell-Mediated Immune Responses to -Expressed and Stage-Specific Antigens in Latent and Active Tuberculosis Across Different Age Groups.

Front Immunol. 2020

[4]
PD-1 Expression on -Specific CD4 T Cells Is Associated With Bacterial Load in Human Tuberculosis.

Front Immunol. 2018-8-31

[5]
Impact of antiretroviral and tuberculosis therapies on CD4 and CD8 HIV/M. tuberculosis-specific T-cell in co-infected subjects.

Immunol Lett. 2018-4-7

[6]
Functional capacity of Mycobacterium tuberculosis-specific T cell responses in humans is associated with mycobacterial load.

J Immunol. 2011-7-20

[7]
Clonal analysis of the T-cell response to in vivo expressed Mycobacterium tuberculosis protein Rv2034, using a CD154 expression based T-cell cloning method.

PLoS One. 2014-6-6

[8]
Characterizing Early T Cell Responses in Nonhuman Primate Model of Tuberculosis.

Front Immunol. 2021

[9]
The source of Mycobacterium tuberculosis-specific IFN-γ production in peripheral blood mononuclear cells of TB patients.

Int Immunopharmacol. 2016-3

[10]
[Dynamic analysis of tuberculosis specific mononuclear cells in peripheral blood of HIV patients with tuberculosis].

Zhonghua Jie He He Hu Xi Za Zhi. 2022-11-12

本文引用的文献

[1]
Development of treatment-decision algorithms for children evaluated for pulmonary tuberculosis: an individual participant data meta-analysis.

Lancet Child Adolesc Health. 2023-5

[2]
Diagnosis of paediatric tuberculosis by optically detecting two virulence factors on extracellular vesicles in blood samples.

Nat Biomed Eng. 2022-8

[3]
IFN-γ-independent control of M. tuberculosis requires CD4 T cell-derived GM-CSF and activation of HIF-1α.

PLoS Pathog. 2022-7

[4]
CRISPR detection of circulating cell-free Mycobacterium tuberculosis DNA in adults and children, including children with HIV: a molecular diagnostics study.

Lancet Microbe. 2022-7

[5]
Tuberculous Meningitis in Children: A Forgotten Public Health Emergency.

Front Neurol. 2022-3-17

[6]
Isolation of Peripheral Blood Mononuclear Cells Using Vacutainer Cellular Preparation Tubes (CPT).

Bio Protoc. 2017-1-20

[7]
Incident Tuberculosis Diagnoses in Children at High Risk for Disease.

Open Forum Infect Dis. 2021-2-18

[8]
Vaccine-Induced CD8 T Cell Responses in Children: A Review of Age-Specific Molecular Determinants Contributing to Antigen Cross-Presentation.

Front Immunol. 2020-12-23

[9]
The risk of tuberculosis in children after close exposure: a systematic review and individual-participant meta-analysis.

Lancet. 2020-3-21

[10]
Recognition of CD8 T-cell epitopes to identify adults with pulmonary tuberculosis.

Eur Respir J. 2019-5-30

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