Immune Phenotype and Functionality of <i>Mtb-</i>Specific<i> </i>T-Cells in HIV/TB Co-Infected Patients on Antiretroviral Treatment
Lucy Mupfumi,
Cheleka A.M. Mpande,
Tim Reid,
Sikhulile Moyo,
Sanghyuk S. Shin,
Nicola Zetola,
Tuelo Mogashoa,
Rosemary M. Musonda,
Ishmael Kasvosve,
Thomas J. Scriba,
Elisa Nemes,
Simani Gaseitsiwe
Affiliations
Lucy Mupfumi
Department of Medical Laboratory Sciences, Faculty of Health Sciences, University of Botswana, Gaborone 4775, Botswana
Cheleka A.M. Mpande
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town 7935, South Africa
Tim Reid
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town 7935, South Africa
Sikhulile Moyo
Botswana Harvard AIDS Institute Partnership, Gaborone 320, Botswana
Sanghyuk S. Shin
Sue & Bill Gross School of Nursing, University of California Irvine, Irvine CA 92697, USA
Nicola Zetola
Infectious Diseases Division, University of Pennsylvania, Philadelphia, Pennsylvania, USA & Botswana-Upenn Partnership, Gaborone, Botswana
Tuelo Mogashoa
Department of Medical Laboratory Sciences, Faculty of Health Sciences, University of Botswana, Gaborone 4775, Botswana
Rosemary M. Musonda
Botswana Harvard AIDS Institute Partnership, Gaborone 320, Botswana
Ishmael Kasvosve
Department of Medical Laboratory Sciences, Faculty of Health Sciences, University of Botswana, Gaborone 4775, Botswana
Thomas J. Scriba
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town 7935, South Africa
Elisa Nemes
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town 7935, South Africa
Simani Gaseitsiwe
Botswana Harvard AIDS Institute Partnership, Gaborone 320, Botswana
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.
