title: Reduced T(H)1/T(H)17 CD4 T-cell numbers are associated with impaired purified protein derivative-specific cytokine responses in patients with HIV-1 infection.
abstract: BACKGROUND
  In HIV-1-infected patients impaired IFN-γ responses to purified protein derivative (PPD) are associated with an increased risk of active tuberculosis. Tuberculosis antigen-specific cells are found in the T(H)1/T(H)17 subset of CD4 T cells, which support HIV-1 replication. Selective loss of T(H)1/T(H)17 cells in patients with HIV-1 infection might contribute to reduced tuberculosis-induced immune responses and an increased susceptibility to active tuberculosis.
  
  
  OBJECTIVE
  We sought to investigate the association between T(H)1/T(H)17 cells and PPD-specific cytokine responses in HIV-1-infected patients.
  
  
  METHODS
  A cross-sectional study was performed on healthy control subjects, HIV-1-infected patients receiving successful antiretroviral therapy (ART(+)), and ART-naive HIV-1-infected patients (ART(-)). All patients studied had evidence of BCG vaccination. Four discrete CD4 T-cell subsets were assessed by flow cytometry: T(H)1/T(H)17 cells (CXCR3(+)CCR6(+)CCR4(-)), T(H)1 cells (CXCR3(+)CCR6(-)CCR4(-)), T(H)17 cells (CXCR3(-)CCR6(+)CCR4(+)), and T(H)2 cells (CXCR3(-)CCR6(-)CCR4(+)). IFN-γ and IL-2 PPD-specific cytokine responses were assessed in PBMCs by using the enzyme-linked immunospot assay.
  
  
  RESULTS
  Twenty-nine healthy control subjects, 34 ART(+) patients, and 26 ART(-) patients were recruited. The number and frequency of T(H)1/T(H)17 and T(H)1/T(H)17 CCR5(+) CD4 T cells were significantly reduced in HIV-1-infected patients. IFN-γ and IL-2 PPD responses were significantly lower in ART(-) patients and were partially reconstituted with successful ART. Loss of T(H)1/T(H)17 CCR5(+) cells was associated with reduced IFN-γ and IL-2 PPD responses.
  
  
  CONCLUSIONS
  Selective loss of T(H)1/T(H)17 cells may be a risk factor for the development of active tuberculosis in patients with HIV-1 infection and might be a useful biomarker in the development of tuberculosis vaccines.
authors: Immunology Section, Division of Infectious Diseases, Imperial College, Chelsea & Westminster Hospital Campus, London, UK.
authors: Sally
authors: S
authors: Clark
authors: Emma
authors: E
authors: Page
authors: Tom
authors: T
authors: Ford
authors: Rebecca
authors: R
authors: Metcalf
authors: Anton
authors: A
authors: Pozniak
authors: Mark
authors: M
authors: Nelson
authors: Donald C
authors: DC
authors: Henderson
authors: David
authors: D
authors: Asboe
authors: Frances
authors: F
authors: Gotch
authors: Brian G
authors: BG
authors: Gazzard
authors: Peter
authors: P
authors: Kelleher
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000276:immunology*; D000328:Adult; D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D003430:Cross-Sectional Studies; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D014373:Tuberculin / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*
chemical_list: D015415:Biomarkers; C508594:IL2 protein, human; D007376:Interleukin-2; D014373:Tuberculin; D007371:Interferon-gamma