Hepatitis C Virus Affects Tuberculosis-Specific T Cells in HIV-Negative Patients

Abstract

The occurrence of tuberculosis (TB) and hepatitis C virus (HCV) infections in the same patient presents a unique clinical challenge. The impact of HCV infection on the immune response to TB remains poorly investigated in TB⁺/HCV⁺ patients. This study was conducted to evaluate the impact of HCV on the T-cell-mediated immune response to TB in coinfected patients. Sixty-four patients with active TB infections were screened for coinfection with HCV. The expression of immune activation markers IFN-γ, CD38, and HLA-DR on TB-specific CD4⁺ T cells was evaluated by flow cytometry in TB-monoinfected patients, TB/HCV-coinfected patients, and healthy controls. IL-2, IL-4, IFN-γ, TNF-α, and IL-10 levels were measured using ELISA. The end-of-treatment response to anti-TB therapy was recorded for both patient groups. Significantly lower levels of CD4⁺IFN-γ⁺CD38⁺ and CD4⁺IFN-γ⁺HLA-DR⁺ T cells were detected in TB/HCV-coinfected patients compared to TB monoinfected patients and controls. TB⁺/HCV⁺-coinfected patients showed higher serum levels of IL-10. The baseline frequencies of TB-specific activated T-cell subsets did not predict the response to antituberculous therapy in TB⁺/HCV⁺ patients. We concluded that different subsets of TB-specific CD4⁺ T cells in TB/HCV-infected individuals are partially impaired in early-stage HCV infection. This was combined with increased serum IL-10 level. Such immune modulations may represent a powerful risk factor for disease progression in patients with HCV/TB coinfection.

Keywords: IL-10; T cells; TB/HCV coinfection; hepatitis C virus; tuberculosis.

Figure 1

Frequencies of different T-cell subsets in different study groups. (A) Representative gating strategy for identifying T-cell subsets. Gray-filled histograms represent isotype controls. (B–H) Differences in frequency of different T cells expressing activation markers CD38, HLA-DR, or IFN-γ. Column bars represent median ± interquartile range; p-values were calculated using Mann–Whitney U-test.

Figure 1

Frequencies of different T-cell subsets in different study groups. (A) Representative gating strategy for identifying T-cell subsets. Gray-filled histograms represent isotype controls. (B–H) Differences in frequency of different T cells expressing activation markers CD38, HLA-DR, or IFN-γ. Column bars represent median ± interquartile range; p-values were calculated using Mann–Whitney U-test.