Journal
FRONTIERS IN IMMUNOLOGY
Volume 8, Issue -, Pages 1-11Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2017.00968
Keywords
Mycobacterium tuberculosis; HIV; latent tuberculosis infection; active tuberculosis; Mycobacterium tuberculosis-specific CD4 response
Categories
Funding
- National Research Foundation of South Africa (NRF) [92558]
- Poliomyelitis Research Foundation (PRF) [14/20]
- National Institutes of Health, the Office of the Director (OD) (NIH) [R21AI115977]
- Wellcome Trust [104803, 203135]
- European Union [FP7-Health-F3-2012-305578, 643381]
- Cancer Research UK [FC00110218]
- UK Medical Research Council [FC00110218]
- National Institutes of Health [U01AI115940]
- Medical Research Council of South Africa via its strategic health innovations partnerships
- National Research Foundation of South Africa [96841]
- MRC [MC_U117588499] Funding Source: UKRI
- Medical Research Council [MC_U117588499] Funding Source: researchfish
- The Francis Crick Institute [10218] Funding Source: researchfish
- Wellcome Trust [104803/Z/14/Z] Funding Source: researchfish
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Several immune-based assays have been suggested to differentiate latent from active tuberculosis (TB). However, their relative performance as well as their efficacy in HIV-infected persons, a highly at-risk population, remains unclear. In a study of 81 individuals, divided into four groups based on their HIV-1 status and TB disease activity, we compared the differentiation (CD27 and KLRG1), activation (HLA-DR), homing potential (CCR4, CCR6, CXCR3, and CD161) and functional profiles (IFN gamma, IL-2, and TNF alpha) of Mycobacterium tuberculosis (Mtb)-specific CD4+ T cells using flow cytometry. Active TB disease induced major changes within the Mtb-responding CD4+ T cell population, promoting memory maturation, elevated activation and increased inflammatory potential when compared to individuals with latent TB infection. Moreover, the functional profile of Mtb-specific CD4+ T cells appeared to be inherently related to their degree of differentiation. While these specific cell features were all capable of discriminating latent from active TB, irrespective of HIV status, HLA-DR expression showed the best performance for TB diagnosis [area-under-the-curve (AUC) = 0.92, 95% CI: 0.82-1.01, specificity: 82%, sensitivity: 84% for HIV- and AUC = 0.99, 95% CI: 0.98-1.01, specificity: 94%, sensitivity: 93% for HIV+]. In conclusion, these data support the idea that analysis of T cell phenotype can be diagnostically useful in TB.
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