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

• Mycobacterium tuberculosis (Mtb)-specific polyfunctional CD4 associated with active TB–HIV.
• Mtb-specific IFNγ+ TNFα+ CD4 T-cells associate with active TB–HIV.
• Mtb-specific IL2+ TNFα+ CD4 T-cells associate with HIV–LTBI.
• CD4+ T-cell response presented an effector-memory status in active TB–HIV.
• Mtb-specific monofunctional CD8 T-cells are higher than polyfunctional cells.

SummaryObjectivesPolyfunctional 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)-naïve HIV-infected patients from a low TB-endemic country.MethodsWe 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.ResultsThe 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, IFNγ+ TNFα+ CD4+ T-cells associated with HIV–TB (p ≤ 0.02) whereas IL2+ TNFα+ 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.ConclusionsIn HIV-infection, polyfunctional CD4+ T-cell-response associates with active TB, characterized by a high proportion of IFNγ+ TNFα+ and an effector-memory phenotype.

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