Human immunodeficiency virus infection impairs Th1 and Th17 Mycobacterium tuberculosis–specific T-cell responses
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+...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Oxford University Press
2018
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| _version_ | 1826263883983093760 |
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| author | Murray, L Satti, I Meyerowitz, J Jones, M Willberg, C Ussher, J Goedhals, D Hurst, J Phillips, R McShane, H Vuuren, C Frater, J |
| author_facet | Murray, L Satti, I Meyerowitz, J Jones, M Willberg, C Ussher, J Goedhals, D Hurst, J Phillips, R McShane, H Vuuren, C Frater, J |
| author_sort | Murray, L |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T19:58:57Z |
| format | Journal article |
| id | oxford-uuid:269cb154-e327-4fce-b976-de2e12ec981e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:58:57Z |
| publishDate | 2018 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:269cb154-e327-4fce-b976-de2e12ec981e2022-03-26T12:02:01ZHuman immunodeficiency virus infection impairs Th1 and Th17 Mycobacterium tuberculosis–specific T-cell responsesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:269cb154-e327-4fce-b976-de2e12ec981eEnglishSymplectic Elements at OxfordOxford University Press2018Murray, LSatti, IMeyerowitz, JJones, MWillberg, CUssher, JGoedhals, DHurst, JPhillips, RMcShane, HVuuren, CFrater, JHuman 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. |
| spellingShingle | Murray, L Satti, I Meyerowitz, J Jones, M Willberg, C Ussher, J Goedhals, D Hurst, J Phillips, R McShane, H Vuuren, C Frater, J Human immunodeficiency virus infection impairs Th1 and Th17 Mycobacterium tuberculosis–specific T-cell responses |
| title | Human immunodeficiency virus infection impairs Th1 and Th17 Mycobacterium tuberculosis–specific T-cell responses |
| title_full | Human immunodeficiency virus infection impairs Th1 and Th17 Mycobacterium tuberculosis–specific T-cell responses |
| title_fullStr | Human immunodeficiency virus infection impairs Th1 and Th17 Mycobacterium tuberculosis–specific T-cell responses |
| title_full_unstemmed | Human immunodeficiency virus infection impairs Th1 and Th17 Mycobacterium tuberculosis–specific T-cell responses |
| title_short | Human immunodeficiency virus infection impairs Th1 and Th17 Mycobacterium tuberculosis–specific T-cell responses |
| title_sort | human immunodeficiency virus infection impairs th1 and th17 mycobacterium tuberculosis specific t cell responses |
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