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. OBJECTIVES: 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.