K Ghazal1, O Morales2, C Barjon3, G Dahlqvist4, L Aoudjehane5, L Ouaguia2, N Delhem2, F Conti6. 1. Sorbonne Universités, UPMC Université Paris 06, INSERM, UMR_S 938, Saint-Antoine Research Center, 75012 Paris, France; AP-HP, Bicêtre Hospital, Biochemistry Laboratory, 94275 Le Kremlin-Bicêtre cedex, France. Electronic address: khaldounghazal@gmail.com. 2. CNRS, UMR8161, Institut de Biologie de Lille, Université de Lille, Institut Pasteur de Lille, IFR 142, 59021 Lille cedex, France. 3. Sorbonne Universités, UPMC Université Paris 06, INSERM, UMR_S 938, Saint-Antoine Research Center, 75012 Paris, France; De Duve Institute, Université catholique de Louvain, 1200 Brussels, Belgium. 4. Sorbonne Universités, UPMC Université Paris 06, INSERM, UMR_S 938, Saint-Antoine Research Center, 75012 Paris, France; Cliniques Universitaires Saint-Luc, 1200 Woluwe-Saint-Lambert, Belgium. 5. Sorbonne Universités, UPMC Université Paris 06, INSERM, UMR_S 938, Saint-Antoine Research Center, 75012 Paris, France; Institute of Cardiometabolism and Nutrition (ICAN), 75013 Paris, France. 6. Sorbonne Universités, UPMC Université Paris 06, INSERM, UMR_S 938, Saint-Antoine Research Center, 75012 Paris, France; AP-HP, Pitié-Salpêtrière hospital, Unité Médicale de Transplantation Hépatique, 75013 Paris, France.
Abstract
BACKGROUND: Immune response failure against hepatitis C virus (HCV) has been associated with an increased regulatory T cell (Treg) activity. After liver transplantation (LT), 80% of patients experience an accelerated progression of hepatitis C recurrence. The aim of this work was to assess the involvement of Tregs, T helper (Th) 1, 2 and 17 cells in recurrent hepatitis C. METHODS: Peripheral blood cells obtained before and one month after LT from 22 recipients were analysed. Forty-four key molecules related to Treg, Th1, 2 and 17 responses, were evaluated using qRT-PCR. Liver recipients were classified in two groups according to graft fibrosis evaluated by the METAVIR score on the biopsy performed one year after LT (mild: F ≤ 1, n = 13; severe: F > 1, n = 9). Patients developing a severe recurrence were compared with patients with a mild recurrence. RESULTS: mRNA levels of Treg markers obtained one month after LT were significantly increased in patients with a severe disease course when compared to patients with a mild recurrence. Markers of the Th1 response were elevated in the same group. No differences in the markers determined before LT were observed. CONCLUSION: These findings suggest that Treg, induced by a multifactorial process, which could include a strong Th1 response itself, may play a role in suppressing the early antiviral response, leading to a severe recurrence of hepatitis C.
BACKGROUND: Immune response failure against hepatitis C virus (HCV) has been associated with an increased regulatory T cell (Treg) activity. After liver transplantation (LT), 80% of patients experience an accelerated progression of hepatitis C recurrence. The aim of this work was to assess the involvement of Tregs, T helper (Th) 1, 2 and 17 cells in recurrent hepatitis C. METHODS: Peripheral blood cells obtained before and one month after LT from 22 recipients were analysed. Forty-four key molecules related to Treg, Th1, 2 and 17 responses, were evaluated using qRT-PCR. Liver recipients were classified in two groups according to graft fibrosis evaluated by the METAVIR score on the biopsy performed one year after LT (mild: F ≤ 1, n = 13; severe: F > 1, n = 9). Patients developing a severe recurrence were compared with patients with a mild recurrence. RESULTS: mRNA levels of Treg markers obtained one month after LT were significantly increased in patients with a severe disease course when compared to patients with a mild recurrence. Markers of the Th1 response were elevated in the same group. No differences in the markers determined before LT were observed. CONCLUSION: These findings suggest that Treg, induced by a multifactorial process, which could include a strong Th1 response itself, may play a role in suppressing the early antiviral response, leading to a severe recurrence of hepatitis C.
Authors: Yara O Aghabi; Alia Yasin; James I Kennedy; Scott P Davies; Amber E Butler; Zania Stamataki Journal: Front Immunol Date: 2021-04-19 Impact factor: 8.786