title: Polyfunctional T-cells and effector memory phenotype are associated with active TB in HIV-infected patients.
abstract: OBJECTIVE
  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)-naïve 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, 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.
  
  
  CONCLUSIONS
  In HIV-infection, polyfunctional CD4(+) T-cell-response associates with active TB, characterized by a high proportion of IFNγ(+) TNFα(+) and an effector-memory phenotype.
authors: Translational Research Unit, Department of Epidemiology and Preclinical Research, "L. Spallanzani" National Institute for Infectious Diseases (INMI), IRCCS, Via Portuense 292, 00149 Rome, Italy.
authors: Teresa
authors: T
authors: Chiacchio
authors: Translational Research Unit, Department of Epidemiology and Preclinical Research, "L. Spallanzani" National Institute for Infectious Diseases (INMI), IRCCS, Via Portuense 292, 00149 Rome, Italy.
authors: Elisa
authors: E
authors: Petruccioli
authors: Translational Research Unit, Department of Epidemiology and Preclinical Research, "L. Spallanzani" National Institute for Infectious Diseases (INMI), IRCCS, Via Portuense 292, 00149 Rome, Italy.
authors: Valentina
authors: V
authors: Vanini
authors: Translational Research Unit, Department of Epidemiology and Preclinical Research, "L. Spallanzani" National Institute for Infectious Diseases (INMI), IRCCS, Via Portuense 292, 00149 Rome, Italy.
authors: Gilda
authors: G
authors: Cuzzi
authors: Clinical Department, INMI, Rome, Italy.
authors: Carmela
authors: C
authors: Pinnetti
authors: Clinical Department, INMI, Rome, Italy.
authors: Alessandro
authors: A
authors: Sampaolesi
authors: Clinical Department, INMI, Rome, Italy.
authors: Andrea
authors: A
authors: Antinori
authors: Department of Epidemiology and Preclinical Research, INMI, Rome, Italy.
authors: Enrico
authors: E
authors: Girardi
authors: Translational Research Unit, Department of Epidemiology and Preclinical Research, "L. Spallanzani" National Institute for Infectious Diseases (INMI), IRCCS, Via Portuense 292, 00149 Rome, Italy. Electronic address: delia.goletti@inmi.it.
authors: Delia
authors: D
authors: Goletti
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000097:blood / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D055985:Latent Tuberculosis / Q000150:complications / Q000276:immunology*; D008297:Male; D009169:Mycobacterium tuberculosis; D010641:Phenotype; D011446:Prospective Studies; D014376:Tuberculosis / Q000150:complications / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: HIV; LTBI; Phenotype; Polyfunctional; Tuberculosis