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Polyfunctional CD4+ and CD8+ T Cell Responses to Tuberculosis Antigens in HIV-1–Infected Patients before and after Anti-Retroviral Treatment

Jayne S. Sutherland, James M. Young, Kevin L. Peterson, Bakary Sanneh, Hilton C. Whittle, Sarah L. Rowland-Jones, Richard A. Adegbola, Assan Jaye and Martin O. C. Ota
J Immunol April 30, 2010, ji_1000399; DOI: https://doi.org/10.4049/jimmunol.1000399
Jayne S. Sutherland
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James M. Young
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Kevin L. Peterson
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Bakary Sanneh
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Hilton C. Whittle
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Sarah L. Rowland-Jones
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Richard A. Adegbola
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Assan Jaye
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Martin O. C. Ota
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Abstract

Tuberculosis (TB) kills 2 million people per year and infection with HIV is the most potent known risk factor for progression to active TB. An understanding of the immune response to TB Ags in HIV-infected patients is required to develop optimal TB vaccines and diagnostics. We assessed polyfunctional (IFN-γ+IL-2+TNF-α+) T cell responses to TB Ags in three groups of HIV-1–infected patients dependent on their TB status, CD4 counts, and anti-retroviral exposure. We found that although the proportion of IFN-γ cells in response to TB Ags was higher in patients with low CD4 counts, the responding cells changed from a polyfunctional CD4+ to a monofunctional CD8+ response. The overall polyfunctionality of the cells was restored by 12 mo of anti-retroviral therapy and primarily involved CD4+ T cells with an effector memory phenotype. These findings have major implications for diagnosis of TB and in vaccine development strategies for TB in HIV-1–infected patients.

Footnotes

  • This work was supported by the Medical Research Council (U.K.), The Gambia, and the Bill and Melinda Gates Foundation as part of the Grand Challenges for Global Health 6: Biomarkers for TB (WP3).

  • Received February 4, 2010.
  • Accepted March 30, 2010.
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The Journal of Immunology: 209 (1)
The Journal of Immunology
Vol. 209, Issue 1
1 Jul 2022
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Polyfunctional CD4+ and CD8+ T Cell Responses to Tuberculosis Antigens in HIV-1–Infected Patients before and after Anti-Retroviral Treatment
Jayne S. Sutherland, James M. Young, Kevin L. Peterson, Bakary Sanneh, Hilton C. Whittle, Sarah L. Rowland-Jones, Richard A. Adegbola, Assan Jaye, Martin O. C. Ota
The Journal of Immunology April 30, 2010, ji_1000399; DOI: 10.4049/jimmunol.1000399

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Polyfunctional CD4+ and CD8+ T Cell Responses to Tuberculosis Antigens in HIV-1–Infected Patients before and after Anti-Retroviral Treatment
Jayne S. Sutherland, James M. Young, Kevin L. Peterson, Bakary Sanneh, Hilton C. Whittle, Sarah L. Rowland-Jones, Richard A. Adegbola, Assan Jaye, Martin O. C. Ota
The Journal of Immunology April 30, 2010, ji_1000399; DOI: 10.4049/jimmunol.1000399
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