Journal article
Human immunodeficiency virus infection impairs Th1 and Th17 Mycobacterium tuberculosis–specific T-cell responses
- Abstract:
- Human immunodeficiency virus (HIV)-infected individuals have a higher risk of developing active tuberculosis (TB) than HIV-uninfected individuals, but the mechanisms underpinning this are unclear. We hypothesized that depletion of specific components of Mycobacterium tuberculosis (Mtb)-specific CD4+ and CD8+ T-cell responses contributed to this increased risk.Mtb-specific T-cell responses in 147 HIV-infected and 44 HIV-uninfected control subjects in a TB-endemic setting in Bloemfontein, South Africa, were evaluated. Using a whole-blood flow cytometry assay, we measured expression of interferon gamma, tumor necrosis factor alpha, interleukin 2, and interleukin 17 in CD4+ and CD8+ T cells in response to Mtb antigens (PPD, ESAT-6/CFP-10 [EC], and DosR regulon-encoded α-crystallin [Rv2031c]).Fewer HIV-infected individuals had detectable CD4+ and CD8+ T-cell responses to PPD and Rv2031c than HIV-uninfected subjects. Mtb-specific T cells showed distinct patterns of cytokine expression comprising both Th1 (CD4 and CD8) and Th17 (CD4) cytokines, the latter at highest frequency for Rv2031c. Th17 antigen-specific responses to all antigens tested were specifically impaired in HIV-infected individuals.HIV-associated impairment of CD4+ and CD8+Mtb-specific T-cell responses is antigen specific, particularly impacting responses to PPD and Rv2031c. Preferential depletion of Th17 cytokine-expressing CD4+ T cells suggests this T-cell subset may be key to TB susceptibility in HIV-infected individuals.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 2.6MB, Terms of use)
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- Publisher copy:
- 10.1093/infdis/jiy052
Authors
- Publisher:
- Oxford University Press
- Journal:
- Journal of Infectious Diseases More from this journal
- Volume:
- 217
- Issue:
- 11
- Pages:
- 1782–1792
- Publication date:
- 2018-03-13
- Acceptance date:
- 2018-03-09
- DOI:
- EISSN:
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1537-6613
- ISSN:
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0022-1899
- Pmid:
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29546381
- Language:
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English
- Keywords:
- Pubs id:
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pubs:830325
- UUID:
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uuid:269cb154-e327-4fce-b976-de2e12ec981e
- Local pid:
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pubs:830325
- Source identifiers:
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830325
- Deposit date:
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2018-03-22
- ARK identifier:
Terms of use
- Copyright holder:
- Murray et al
- Copyright date:
- 2018
- Notes:
-
Copyright © 2018 The Authors. Published by Oxford University Press for the Infectious Diseases Society of America.
This is an Open Access article distributed under the terms of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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