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Transcriptomic analysis of CD4 T cells reveals novel immune signatures of latent tuberculosis

Transcriptomic analysis of CD4 T cells reveals novel immune signatures of latent tuberculosis
Transcriptomic analysis of CD4 T cells reveals novel immune signatures of latent tuberculosis

In the context of infectious diseases, cell population transcriptomics are useful to gain mechanistic insight into protective immune responses, which is not possible using traditional whole-blood approaches. In this study, we applied a cell population transcriptomics strategy to sorted memory CD4 T cells to define novel immune signatures of latent tuberculosis infection (LTBI) and gain insight into the phenotype of tuberculosis (TB)-specific CD4 T cells. We found a 74-gene signature that could discriminate between memory CD4 T cells from healthy latently Mycobacterium tuberculosis-infected subjects and noninfected controls. The gene signature presented a significant overlap with the gene signature of the Th1* (CCR6+CXCR3+CCR4-) subset of CD4 T cells, which contains the majority of TB-specific reactivity and is expanded in LTBI. In particular, three Th1* genes (ABCB1, c-KIT, and GPA33) were differentially expressed at the RNA and protein levels in memory CD4 T cells of LTBI subjects compared with controls. The 74-gene signature also highlighted novel phenotypic markers that further defined the CD4 T cell subset containing TB specificity. We found the majority of TB-specific epitope reactivity in the CD62L-GPA33- Th1* subset. Thus, by combining cell population transcriptomics and single-cell protein-profiling techniques, we identified a CD4 T cell immune signature of LTBI that provided novel insights into the phenotype of TB-specific CD4 T cells.

Journal Article
0022-1767
3283-3290
Burel, Julie G.
d043b967-6296-4f02-b628-e397a82de132
Lindestam Arlehamn, Cecilia S.
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Khan, Nabeela
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Seumois, Grégory
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Greenbaum, Jason A.
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Taplitz, Randy
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Gilman, Robert H.
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Saito, Mayuko
de3e8fc4-9321-4fab-8f4e-1d8660cf7ae3
Vijayanand, Pandurangan
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Sette, Alessandro
240988b3-3c05-4041-a39b-8be8e145803c
Peters, Bjoern
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Burel, Julie G.
d043b967-6296-4f02-b628-e397a82de132
Lindestam Arlehamn, Cecilia S.
972358b3-c46c-4de5-b7e1-afa2cf65ed35
Khan, Nabeela
8dac913b-30ec-4b59-a19b-0857f73d27ed
Seumois, Grégory
0be7d3d6-5526-458c-aa5c-cce52410a2ed
Greenbaum, Jason A.
46c95e55-7187-4f85-ba70-60945eefdbb8
Taplitz, Randy
2d810857-e357-49ea-949e-ea6b7c42cb9d
Gilman, Robert H.
d948b282-8e0c-43de-aeda-4b8c8a789870
Saito, Mayuko
de3e8fc4-9321-4fab-8f4e-1d8660cf7ae3
Vijayanand, Pandurangan
79514f33-66cf-47cc-a8fa-46bbfc21b7d1
Sette, Alessandro
240988b3-3c05-4041-a39b-8be8e145803c
Peters, Bjoern
c49863c8-d2c6-4db4-9d2c-72a7c0cbe117

Burel, Julie G., Lindestam Arlehamn, Cecilia S., Khan, Nabeela, Seumois, Grégory, Greenbaum, Jason A., Taplitz, Randy, Gilman, Robert H., Saito, Mayuko, Vijayanand, Pandurangan, Sette, Alessandro and Peters, Bjoern (2018) Transcriptomic analysis of CD4 T cells reveals novel immune signatures of latent tuberculosis. The Journal of Immunology, 200 (9), 3283-3290. (doi:10.4049/jimmunol.1800118).

Record type: Article

Abstract

In the context of infectious diseases, cell population transcriptomics are useful to gain mechanistic insight into protective immune responses, which is not possible using traditional whole-blood approaches. In this study, we applied a cell population transcriptomics strategy to sorted memory CD4 T cells to define novel immune signatures of latent tuberculosis infection (LTBI) and gain insight into the phenotype of tuberculosis (TB)-specific CD4 T cells. We found a 74-gene signature that could discriminate between memory CD4 T cells from healthy latently Mycobacterium tuberculosis-infected subjects and noninfected controls. The gene signature presented a significant overlap with the gene signature of the Th1* (CCR6+CXCR3+CCR4-) subset of CD4 T cells, which contains the majority of TB-specific reactivity and is expanded in LTBI. In particular, three Th1* genes (ABCB1, c-KIT, and GPA33) were differentially expressed at the RNA and protein levels in memory CD4 T cells of LTBI subjects compared with controls. The 74-gene signature also highlighted novel phenotypic markers that further defined the CD4 T cell subset containing TB specificity. We found the majority of TB-specific epitope reactivity in the CD62L-GPA33- Th1* subset. Thus, by combining cell population transcriptomics and single-cell protein-profiling techniques, we identified a CD4 T cell immune signature of LTBI that provided novel insights into the phenotype of TB-specific CD4 T cells.

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More information

Accepted/In Press date: 1 March 2018
e-pub ahead of print date: 23 April 2018
Published date: 1 May 2018
Additional Information: Copyright © 2018 by The American Association of Immunologists, Inc.
Keywords: Journal Article

Identifiers

Local EPrints ID: 422732
URI: http://eprints.soton.ac.uk/id/eprint/422732
ISSN: 0022-1767
PURE UUID: 65209843-9845-4f6b-835d-9ece0d0434c4

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Date deposited: 01 Aug 2018 16:30
Last modified: 16 Dec 2019 18:05

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Contributors

Author: Julie G. Burel
Author: Cecilia S. Lindestam Arlehamn
Author: Nabeela Khan
Author: Grégory Seumois
Author: Jason A. Greenbaum
Author: Randy Taplitz
Author: Robert H. Gilman
Author: Mayuko Saito
Author: Pandurangan Vijayanand
Author: Alessandro Sette
Author: Bjoern Peters

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