Cd4 T-Cell Cytokine Correlates Of Diagnostic Tests For Latent Tuberculous Infection In Hiv-1-Infected Subjects

SETTING: Public human immunodeficiency virus (HIV) clinic and tuberculosis (TB) clinics in Kampala, Uganda.OBJECTIVE: To examine TB-specific CD4 T-cell single and polyfunctional cytokine correlates of clinical diagnostic tests for latent tuberculous infection (LTBI) in HIV-1-infected subjects.DESIGN: Thirty antiretroviral therapy-naive HTV-1-infected adults without active TB disease underwent clinical tuberculin skin test (TST), interferon-gamma release assay (IGRA), and in vitro flow cytometry analysis on cells stimulated with purified protein derivative (PPD) and TB antigens early secreted antigenic target 6 + culture filtrate protein 10 (EC) for frequencies of interleukin (IL) 2, IL-17, interferongamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) expressing cells.RESULTS: PPD-specific CD4 T-cell expression of TNF-alpha and IFN-gamma was higher in the TST-positive than in the TST-negative group. EC-specific CD4 T-cell expression of TNF-alpha and IL-2 was higher in the TST+group than in the TST group. Expression of both PPD and EC-specific expression of IL-2, IFN-gamma and TNE-alpha were greater in IGRA-positive than in IGRA-negative subjects. The TST+group exhibited greater polyfunctionality than the TST group. All cytokine combinations that contained TNF-alpha correlated strongly with TST size.CONCLUSION: While EL-2, IFN-gamma and TNF-alpha correlate with clinical tests of LTBI, TNT-alpha is the dominant cytokine correlating with both TST size and magnitude of IGRA response.