Polyfunctional T-cells and effector memory phenotype are associated with active TB in HIV-infected patients

Objectives: Polyfunctional T-cells associate with chronic viral infection control while their involvement in tuberculosis (TB) is unclear. We evaluated TB-specific polyfunctional T-cell response and memory status in antiretroviral treatment (ART)-naive HIV-infected patients from a low TB-endemic country. Methods: We prospectively enrolled HIV-infected patients, 12 with active TB (HIV-TB) and 15 with latent tuberculosis infection (LTBI). Peripheral blood cells were stimulated with TB antigens (RD1 proteins/peptides), HIV antigens, cytomegalovirus (CMV) and staphylococcal enterotoxin B (SEB) and analyzed by cytometry. Results: The HIV-TB showed a higher frequency of polyfunctional CD4(+) T-cells in response to RD1 antigens than HIV-LTBI (p = 0.007). Among the CD8(+) T-cells, both groups showed a significantly higher frequency of RD1-specific monofunctional cells than polyfunctional cells (p = 0.03). Analyzing the cytokine profile, IFN gamma(+) TNF alpha(+) CD4(+) T-cells associated with HIV-TB (p <= 0.02) whereas IL2(+) TNF alpha(+) associated with HIV-LTBI (p = 0.009). CD4(+) T-cell response presented an effector-memory status in HIV-TB (p = 0.007) and an effector-memory terminally-differentiated phenotype in HIV-LTBI (p = 0.03). CD8(+) T-cell response presented an effector status in HIV-LTBI (p = 0.02). No significant cytokine profile pattern associated with responses to the other stimuli tested. Conclusions: In HIV-infection, polyfunctional CD4(+) T-cell-response associates with active TB, characterized by a high proportion of IFN gamma(+) TNF alpha(+) and an effector-memory phenotype. (C) 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.