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Transcriptional profile of tuberculosis antigen–specific T cells reveals novel multifunctional features

Transcriptional profile of tuberculosis antigen–specific T cells reveals novel multifunctional features
Transcriptional profile of tuberculosis antigen–specific T cells reveals novel multifunctional features
In latent tuberculosis infection (LTBI) spread of the bacteria is contained by a persistent immune response, which includes CD4+ T cells as important contributors. In this study we show that TB-specific CD4+ T cells have a characteristic chemokine expression signature (CCR6+CXCR3+CCR4−), and that the overall number of these cells is significantly increased in LTBI donors compared with healthy subjects. We have comprehensively characterized the transcriptional signature of CCR6+CXCR3+CCR4− cells and found significant differences to conventional Th1, Th17, and Th2 cells, but no major changes between healthy and LTBI donors. CCR6+CXCR3+CCR4− cells display lineage-specific signatures of both Th1 and Th17 cells, but also have a unique gene expression program, including genes associated with susceptibility to TB, enhanced T cell activation, enhanced cell survival, and induction of a cytotoxic program akin to CTL cells. Overall, the gene expression signature of CCR6+CXCR3+CCR4− cells reveals characteristics important for controlling latent TB infections.
0022-1767
2931-2940
Arlehamn, Cecilia Lindestam
5dac6376-6f50-4e7b-b88b-02b5ec21a7f6
Seumois, Gregory
0be7d3d6-5526-458c-aa5c-cce52410a2ed
Gerasimova, Anna
9172f558-68dd-4d71-9e00-ce5314681145
Huang, Charlie
8a8b072e-b4d6-401f-9192-85dba9e4fecc
Fu, Zheng
49cfb3db-16a9-43c7-afe0-a66d239942f5
Yue, Xiaojing
50e8489c-a374-4dfa-bcad-e5c5d5a57c26
Sette, Alessandro
240988b3-3c05-4041-a39b-8be8e145803c
Vijayanand, Pandurangan
79514f33-66cf-47cc-a8fa-46bbfc21b7d1
Peters, Bjoern
c49863c8-d2c6-4db4-9d2c-72a7c0cbe117
Arlehamn, Cecilia Lindestam
5dac6376-6f50-4e7b-b88b-02b5ec21a7f6
Seumois, Gregory
0be7d3d6-5526-458c-aa5c-cce52410a2ed
Gerasimova, Anna
9172f558-68dd-4d71-9e00-ce5314681145
Huang, Charlie
8a8b072e-b4d6-401f-9192-85dba9e4fecc
Fu, Zheng
49cfb3db-16a9-43c7-afe0-a66d239942f5
Yue, Xiaojing
50e8489c-a374-4dfa-bcad-e5c5d5a57c26
Sette, Alessandro
240988b3-3c05-4041-a39b-8be8e145803c
Vijayanand, Pandurangan
79514f33-66cf-47cc-a8fa-46bbfc21b7d1
Peters, Bjoern
c49863c8-d2c6-4db4-9d2c-72a7c0cbe117

Arlehamn, Cecilia Lindestam, Seumois, Gregory, Gerasimova, Anna, Huang, Charlie, Fu, Zheng, Yue, Xiaojing, Sette, Alessandro, Vijayanand, Pandurangan and Peters, Bjoern (2014) Transcriptional profile of tuberculosis antigen–specific T cells reveals novel multifunctional features. The Journal of Immunology, 193 (6), 2931-2940. (doi:10.4049/jimmunol.1401151).

Record type: Article

Abstract

In latent tuberculosis infection (LTBI) spread of the bacteria is contained by a persistent immune response, which includes CD4+ T cells as important contributors. In this study we show that TB-specific CD4+ T cells have a characteristic chemokine expression signature (CCR6+CXCR3+CCR4−), and that the overall number of these cells is significantly increased in LTBI donors compared with healthy subjects. We have comprehensively characterized the transcriptional signature of CCR6+CXCR3+CCR4− cells and found significant differences to conventional Th1, Th17, and Th2 cells, but no major changes between healthy and LTBI donors. CCR6+CXCR3+CCR4− cells display lineage-specific signatures of both Th1 and Th17 cells, but also have a unique gene expression program, including genes associated with susceptibility to TB, enhanced T cell activation, enhanced cell survival, and induction of a cytotoxic program akin to CTL cells. Overall, the gene expression signature of CCR6+CXCR3+CCR4− cells reveals characteristics important for controlling latent TB infections.

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Accepted/In Press date: 5 July 2014
e-pub ahead of print date: 4 August 2014
Published date: 15 September 2014

Identifiers

Local EPrints ID: 436480
URI: http://eprints.soton.ac.uk/id/eprint/436480
ISSN: 0022-1767
PURE UUID: 54d8ae92-8fdf-4c1e-9f06-62fc8444b81a
ORCID for Pandurangan Vijayanand: ORCID iD orcid.org/0000-0001-7067-9723

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Date deposited: 11 Dec 2019 17:30
Last modified: 16 Mar 2024 05:37

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Contributors

Author: Cecilia Lindestam Arlehamn
Author: Gregory Seumois
Author: Anna Gerasimova
Author: Charlie Huang
Author: Zheng Fu
Author: Xiaojing Yue
Author: Alessandro Sette
Author: Pandurangan Vijayanand ORCID iD
Author: Bjoern Peters

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