TY - JOUR
T1 - Immune phenotype and functionality of Mtb-specific T-cells in HIV/TB co-infected patients on antiretroviral treatment
AU - Mupfumi, Lucy
AU - Mpande, Cheleka A.M.
AU - Reid, Tim
AU - Moyo, Sikhulile
AU - Shin, Sanghyuk S.
AU - Zetola, Nicola
AU - Mogashoa, Tuelo
AU - Musonda, Rosemary M.
AU - Kasvosve, Ishmael
AU - Scriba, Thomas J.
AU - Nemes, Elisa
AU - Gaseitsiwe, Simani
N1 - Funding Information:
This work was supported by the sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative (grant # DEL-15-006 to L.M., S.M., T.M., and S.G.), the Fogarty International Center, National Institute of Mental Health and National Institute of Allergy and Infectious Diseases of the National Institutes of Health (grant # D43 TW010543 to S.M. and grant # K01AI118559 to SSS). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)?s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa?s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (grant # 107752/Z/15/Z) and the government of the United Kingdom. R.M. and T.M. were partially supported by the EDCTP2 program Trials of Excellence in Southern Africa (TESA II), supported under Horizon 2020, the European Union. The views expressed in this publication are those of the authors and not necessarily those of the AAS, AESA, NEPAD Agency, Wellcome Trust, National Institutes of Health, or the UK government. The funders had no role in the study design, data collection, and decision to publish or in the preparation of the manuscript. Acknowledgments: We wish to thank Dr One Dintwe from the Cape Town HVTN Immunology Laboratory (CHIL) for the kind donation of the HIV Gag peptides used for the intracellular cytokine-staining assay.
Funding Information:
Funding: This work was supported by the sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative (grant # DEL-15-006 to L.M., S.M., T.M., and S.G.), the Fogarty International Center, National Institute of Mental Health and National Institute of Allergy and Infectious Diseases of the National Institutes of Health (grant # D43 TW010543 to S.M. and grant # K01AI118559 to SSS). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)’s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (grant #107752/Z/15/Z) and the government of the United Kingdom. R.M. and T.M. were partially supported by the EDCTP2 program Trials of Excellence in Southern Africa (TESA II), supported under Horizon 2020, the European Union. The views expressed in this publication are those of the authors and not necessarily those of the AAS, AESA, NEPAD Agency, Wellcome Trust, National Institutes of Health, or the UK government. The funders had no role in the study design, data collection, and decision to publish or in the preparation of the manuscript.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/3
Y1 - 2020/3
N2 - The performance of host blood-based biomarkers for tuberculosis (TB) in HIV-infected patients on antiretroviral therapy (ART) has not been fully assessed. We evaluated the immune phenotype and functionality of antigen-specific T-cell responses in HIV positive (+) participants with TB (n = 12) compared to HIV negative (−) participants with either TB (n = 9) or latent TB infection (LTBI) (n = 9). We show that the cytokine profile of Mtb-specific CD4+ T-cells in participants with TB, regardless of HIV status, was predominantly single IFN-γ or dual IFN-γ/ TNFα. Whilst ESAT-6/CFP-10 responding T-cells were predominantly of an effector memory (CD27−CD45RA−CCR7−) profile, HIV-specific T-cells were mainly of a central (CD27+CD45RA−CCR7+) and transitional memory (CD27+CD45RA+/−CCR7−) phenotype on both CD4+ and CD8+ T-cells. Using receiving operating characteristic (ROC) curve analysis, co-expression of CD38 and HLA-DR on ESAT-6/CFP-10 responding total cytokine-producing CD4+ T-cells had a high sensitivity for discriminating HIV+TB (100%, 95% CI 70–100) and HIV−TB (100%, 95% CI 70–100) from latent TB with high specificity (100%, 95% CI 68–100 for HIV−TB) at a cut-off value of 5% and 13%, respectively. TB treatment reduced the proportion of Mtb-specific total cytokine+CD38+HLA-DR+ CD4+ T-cells only in HIV−TB (p = 0.001). Our results suggest that co-expression of CD38 and HLA-DR on Mtb-specific CD4+ T-cells could serve as a TB diagnosis tool regardless of HIV status.
AB - The performance of host blood-based biomarkers for tuberculosis (TB) in HIV-infected patients on antiretroviral therapy (ART) has not been fully assessed. We evaluated the immune phenotype and functionality of antigen-specific T-cell responses in HIV positive (+) participants with TB (n = 12) compared to HIV negative (−) participants with either TB (n = 9) or latent TB infection (LTBI) (n = 9). We show that the cytokine profile of Mtb-specific CD4+ T-cells in participants with TB, regardless of HIV status, was predominantly single IFN-γ or dual IFN-γ/ TNFα. Whilst ESAT-6/CFP-10 responding T-cells were predominantly of an effector memory (CD27−CD45RA−CCR7−) profile, HIV-specific T-cells were mainly of a central (CD27+CD45RA−CCR7+) and transitional memory (CD27+CD45RA+/−CCR7−) phenotype on both CD4+ and CD8+ T-cells. Using receiving operating characteristic (ROC) curve analysis, co-expression of CD38 and HLA-DR on ESAT-6/CFP-10 responding total cytokine-producing CD4+ T-cells had a high sensitivity for discriminating HIV+TB (100%, 95% CI 70–100) and HIV−TB (100%, 95% CI 70–100) from latent TB with high specificity (100%, 95% CI 68–100 for HIV−TB) at a cut-off value of 5% and 13%, respectively. TB treatment reduced the proportion of Mtb-specific total cytokine+CD38+HLA-DR+ CD4+ T-cells only in HIV−TB (p = 0.001). Our results suggest that co-expression of CD38 and HLA-DR on Mtb-specific CD4+ T-cells could serve as a TB diagnosis tool regardless of HIV status.
KW - CD38
KW - HLA-DR
KW - Immune activation
KW - Treatment response
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U2 - 10.3390/pathogens9030180
DO - 10.3390/pathogens9030180
M3 - Article
AN - SCOPUS:85081226404
VL - 9
JO - Pathogens
JF - Pathogens
SN - 2076-0817
IS - 3
M1 - 180
ER -