Peripheral immune cell profile and activation status in chronic HCV mono- and HCV/HIV co-infected patients

Abstract

Background: Due to similar routes of viral transmission, chronic HCV and HIV co-infection is frequent. Since it has been reported that both viruses perturbs immune homeostasis, our aim was to evaluate the peripheral immune cell moiety in HCV mono- and HCV/HIV co-infected patients to determine if co-infection alters HCV immune profile. Methods & Materials: Liver biopsies (47 = HCV treatment naïve, 13 = HCV/HIV only HAART) and concomitant blood samples were analysed. In peripheral blood: 1) frequency of total T cells(CD3 + ), T helper(Th, CD3 + CD4 + ), cytotoxic T lymphocytes(CTL, CD3 + CD8 + ) and Natural Killer cells(NK, CD3-CD56 + CD16 + ); 2) CTL and Th differentiation status [naïve (CD27 + CD45RA + ), central-memory (CD27 + CD45RA-), effector-memory(CD27-CD45RA-), effector(CD27-CD45RA + ) and activated (DR + )]; 3) frequencies of Th17(CD4 + IL17A + ), Th1(CD4 + IFNg + ) and Treg(CD4 + CD25hiFoxp3 + ) and 4) NK and CTL degranulation activity (CD107a) were evaluated by FACS. Non-infected donors (n = 33) were included. Inflammatory activity and fibrosis were assessed in liver biopsies using the modified Knodell scoring system and METAVIR. Results: While HCV patients did not display differences in lymphocyte frequencies compared to donors, co-infected patients showed the lowest Th(donor vs HCV/HIV p < 0.001, HCV vs HCV/HIV p < 0.001), the highest CTLs(donor vs HCV/HIV p < 0.001, HCV vs HCV/HIV p < 0.001) and the lowest NK(donor vs HCV/HIV p < 0.01, HCV vs HCV/HIV p < 0.05) frequencies. Absolute numbers confirmed these results. Moreover, only Th17 absolute numbers were diminished in co-infection (donor vs HCV/HIV p < 0.05). Regarding T cell differentiation status in HCV patients compared to donors: Th cells showed low naïve (p < 0.01) but high effector memory (p < 0.05) and activated cells (p < 0.01) frequencies; CTL showed low naïve (p < 0.01) but high activated cell (p < 0.01) frequencies. Although, HCV/HIV displayed a similar profile to HCV, Th and CTL activation was higher in HCV/HIV than HCV (p < 0.001). Degranulation activity of CTL and NK cells showed no differences between groups. Concerning to liver damage, any of the evaluated immune cell parameters displayed association with fibrosis or hepatitis severity. Conclusion: Although in chronic HCV infection the lymphocyte frequency was not modified, an altered T cell differentiation profile was evident. The co-infected condition distorted lymphocyte frequencies and enhanced T cell activation. This deteriorated immune profile may condition T cell response against antigens, including vaccines.