Characterization of HCV-specific CD4+Th17 immunity in recurrent hepatitis C-induced liver allograft fibrosis

H. I. Basha, V. Subramanian, A. Seetharam, D. S. Nath, S. Ramachandran, C. D. Anderson, S. Shenoy, W. C. Chapman, J. S. Crippin, T. Mohanakumar

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Hepatitis C virus (HCV) recurrence with accelerated fibrosis following orthotopic liver transplantation (OLT) is a universal phenomenon. To evaluate mechanisms contributing to HCV induced allograft fibrosis/cirrhosis, we investigated HCV-specific CD4+Th17 cells and their induction in OLT recipients with recurrence utilizing 51 HCV+ OLT recipients, 15 healthy controls and 9 HCV- OLT recipients. Frequency of HCV specific CD4+ Tcells secreting IFN-γ, IL-17 and IL-10 was analyzed by ELISpot. Serum cytokines and chemokines were analyzed by LUMINEX. Recipients with recurrent HCV induced allograft inflammation and fibrosis/cirrhosis demonstrated a significant increase in frequency of HCV specific CD4+Th17 cells. Increased pro-inflammatory mediators (IL-17, IL-1β, IL-6, IL-8 and MCP-1), decreased IFN-γ, and increased IL-4, IL-5 and IL-10 levels were identified. OLT recipients with allograft inflammation and fibrosis/cirrhosis demonstrated increased frequency of Foxp3+ regulatory T cells (Tregs) that inhibited HCV specific CD4+Th1 but not Th17 cells. This suggests that recurrent HCV infection in OLT recipients induces an inflammatory milieu characterized by increased IL-6, IL-1β and decreased IFN-γ which facilitates induction of HCV specific CD4+Th17 cells. These cells are resistant to suppression by Tregs and may mediate an inflammatory cascade leading to cirrhosis in OLT recipients following HCV recurrence.

Original languageEnglish
Pages (from-to)775-785
Number of pages11
JournalAmerican Journal of Transplantation
Volume11
Issue number4
DOIs
StatePublished - Apr 1 2011

Keywords

  • Inflammation
  • T cell
  • transplantation
  • viral

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