Early high levels of regulatory T cells and T helper 1 may predict the progression of recurrent hepatitis C after liver transplantation

Clin Res Hepatol Gastroenterol. 2019 Jun;43(3):273-281. doi: 10.1016/j.clinre.2018.10.005. Epub 2019 Jan 31.

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.

Keywords: HCV recurrence; Hepatitis C; Liver transplantation; Regulatory T cells; Th1; Tr1.

MeSH terms

  • Aged
  • Biomarkers / metabolism
  • CD28 Antigens / genetics
  • CD28 Antigens / metabolism
  • CD40 Ligand / genetics
  • CD40 Ligand / metabolism
  • CTLA-4 Antigen / genetics
  • CTLA-4 Antigen / metabolism
  • Disease Progression
  • Female
  • Hepatitis C, Chronic / diagnosis*
  • Humans
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interleukin-10 Receptor alpha Subunit / genetics
  • Interleukin-10 Receptor alpha Subunit / metabolism
  • Interleukin-10 Receptor beta Subunit / genetics
  • Interleukin-10 Receptor beta Subunit / metabolism
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism
  • Interleukin-2 Receptor alpha Subunit / genetics
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Interleukin-23 / genetics
  • Interleukin-23 / metabolism
  • Liver Transplantation*
  • Male
  • Middle Aged
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Recurrence
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism
  • T-Lymphocytes, Helper-Inducer / metabolism*
  • T-Lymphocytes, Regulatory / metabolism*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / genetics
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism

Substances

  • Biomarkers
  • CD28 Antigens
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Interleukin-10 Receptor alpha Subunit
  • Interleukin-10 Receptor beta Subunit
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-23
  • RNA, Messenger
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • CD40 Ligand
  • Interferon-gamma