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- Title
Enhanced ability of regulatory T cells in chronic hepatitis C patients with persistently normal alanine aminotransferase levels than those with active hepatitis.
- Authors
Itose, I.; Kanto, T.; Kakita, N.; Takebe, S.; Inoue, M.; Higashitani, K.; Miyazaki, M.; Miyatake, H.; Sakakibara, M.; Hiramatsu, N.; Takehara, T.; Kasahara, A.; Hayashi, N.
- Abstract
In hepatitis C virus (HCV) infection, the Th1-type immune response is involved in liver injury. A predominance of immunosuppressive regulatory T cells (Treg) is hypothesized in patients with persistently normal alanine aminotransferase (PNALT). Our aim was to clarify the role of Treg in the pathogenesis of PNALT. Fifteen chronically HCV-infected patients with PNALT, 21 with elevated ALT (CH) and 19 healthy subjects (HS) were enrolled. We determined naturally-occurring Treg (N-Treg) as CD4+CD25high+FOXP3+ T cells. The expression of FOXP3 and CTLA4 in CD4+CD25high+ cells was quantified by real-time reverse transcriptase-polymerase chain reaction. Bulk or CD25-depleted CD4+ T cells cultured with HCV-NS5 loaded dendritic cells were assayed for their proliferation and cytokine release. We examined CD127–CD25–FOXP3+ cells as distinct subsets other than CD25+ N-Treg. The frequencies of N-Treg in patients were significantly higher than those in HS. The FOXP3 and CTLA4 transcripts were higher in PNALT than those in CH. The depletion of CD25+ cells enhanced HCV-specific T cell responses, showing that co-existing CD25+ cells are suppressive. Such inhibitory capacity was more potent in PNALT. The frequency of CD4+CD127–CD25–FOXP3+ cells was higher in CH than those in PNALT. Treg are more abundant in HCV-infected patients, and their suppressor ability is more potent in patients with PNALT than in those with active hepatitis.
- Subjects
HEPATITIS; LIVER diseases; LYMPHOCYTES; VIRAL hepatitis; IMMUNE response
- Publication
Journal of Viral Hepatitis, 2009, Vol 16, Issue 12, p844
- ISSN
1352-0504
- Publication type
Article
- DOI
10.1111/j.1365-2893.2009.01131.x