Volume 65, Issue 6, Pages 1261-1263 (December 2016) Reduced CD161+ MAIT cell frequencies in HCV and HIV/HCV co-infection: Is the liver the heart of the matter?  Johanna M. Eberhard, Silke Kummer, Philip Hartjen, Anja Hüfner, Tom Diedrich, Olaf Degen, Ansgar W. Lohse, Jan van Lunzen, Julian Schulze zur Wiesch  Journal of Hepatology  Volume 65, Issue 6, Pages 1261-1263 (December 2016) DOI: 10.1016/j.jhep.2016.07.031 Copyright © 2016 European Association for the Study of the Liver Terms and Conditions

Fig. 1 Determination of CD161+ TCR Vα7.2+ MAIT cell frequencies in HIV, HCV mono- and HIV/HCV co-infection. (A) Representative fluorescence-activated cell sorting (FACS) plots depicting CD161 and TCR Vα7.2 based MAIT cell characterization in the CD4− CD3+ T cell subset from a healthy control, a viremic HIV patient, an HIV patient receiving ART, an HCV/HIV co-infected patient and a chronic HCV patient (B) Cumulative display of CD161+ TCR Vα7.2+ MAIT cell frequencies and CD161−TCR Vα7.2+ cells in% of CD3+ T cells comparing PBMC samples derived from healthy controls (healthy n=26), untreated patients with high HIV loads (HIV high viral load (VL) n=24), patients receiving antiretroviral treatment for a at least one year (HIV ART n=15), HIV/HCV co-infected patients (HIV/HCV n=20) and chronic HCV patients (HCV n=33). All groups were compared by Kruskal-Wallis followed by multiple comparison test. p values smaller than 0.05 were considered significant, where ∗, ∗∗ and ∗∗∗ indicate p values between 0.01 to 0.05, 0.001 to 0.01 and 0.0001 to 0.001, respectively. Bars and lines indicate mean and standard deviation. MAIT cell frequencies were reduced in all groups including HCV patients compared to healthy controls, however most severely in HIV (mean healthy=2.33±1.77 vs. mean HIV high VL=0.65±0.5%, mean HIV ART=0.62±0.64%, mean HIV/HCV=0.65±0.7, mean HCV=1.35±2.2). (C) Longitudinal analysis of CD161± TCR Vα7.2± MAIT cell frequencies in PBMCs from chronic HCV patients (n=7) before after treatment. No significant differences were detected. (D) CD161+ TCR Vα7.2+ MAIT cell frequencies in cells from liver biopsies derived from HIV/ HCV and hepatitis B virus (HBV) uninfected patients (5 NASH liver biopsies, 3 liver biopsies from patients with unclear liver inflammation) compared to liver cells from 5 HCV patients. MAIT cells were reduced in HCV infected livers compared to livers from uninfected controls, (mean uninfected liver=14.7±8.72% vs. mean HCV liver=2.76±2.98%, p=0.0295). (E) The ratio of CD161+ MAIT/CD161− TCR Vα7.2+ cells within the CD3+ T cell population is shifted in HIV and HCV infection. Bars indicate mean frequencies of CD161+ MAIT cells (dark blue) and CD161− TCR Vα7.2+ cells (light blue). (F) Activation of CD161+ MAIT and CD4− T cells was measured as frequency of CD38+ HLA-DR+ CD161+ MAIT cells and was elevated in viremic HIV patients as well as in HIV/HCV co-infected patients and for CD4− T cells also in uninfected liver biopsies. (This figure appears in colour on the web.) Journal of Hepatology 2016 65, 1261-1263DOI: (10.1016/j.jhep.2016.07.031) Copyright © 2016 European Association for the Study of the Liver Terms and Conditions