Immune Phenotype and Functionality of <i>Mtb-</i>Specific<i> </i>T-Cells in HIV/TB Co-Infected Patients on Antiretroviral Treatment
oleh: 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
| Format: | Article |
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| Diterbitkan: | MDPI AG 2020-03-01 |
Deskripsi
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<i> </i>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 <i>Mtb-</i>specific total cytokine+CD38+HLA-DR+ CD4+ T-cells only in HIV−TB (<i>p</i> = 0.001). Our results suggest that co-expression of CD38 and HLA-DR on <i>Mtb-</i>specific CD4+ T-cells could serve as a TB diagnosis tool regardless of HIV status.