期刊
TRANSPLANT IMMUNOLOGY
卷 31, 期 1, 页码 33-41出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.trim.2014.05.006
关键词
Chronic hepatitis C; Living donor liver transplantation; Persistently normal alanine aminotransferase; Regulatory T cell; Sustained viral response; Type 1 regulatory T cells
资金
- MEXT KAKENHI Grant [22590735]
- Japanese Ministry of Education, Culture, Sports, Science, and Technology [22790526]
- Grants-in-Aid for Scientific Research [22790526, 22590735] Funding Source: KAKEN
Introduction: Regulatory T (Treg) and type 1 regulatory T (Tr1) cells facilitate hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT). However, their frequencies and effects on HCV-specific immune responses have not been well investigated. Methods: We determined Treg and Tr1 frequencies in OLT patients with hepatitis C and assessed their associations with HCV-specific T cell responses. These patients comprised the following groups: an early post-transplantation group (n = 14); an OLT-chronic active hepatitis C group (n = 14) with active hepatitis C (alanine aminotransferase of > upper limit of normal/positive for HCV-RNA); an OLT-persistently normal alanine aminotransferase group (n = 12) without active hepatitis C (not interferon/positive for HCV-RNA); and an OLT-sustained viral response group (n = 6) with sustained viral responses using interferon treatment (negative for HCV-RNA). The frequencies of HCV-specific CD4+ T cells that secreted interferon-gamma were determined by enzyme-linked immunosorbent spot assay (except for the OLT early group). Results: Treg and Tr1 frequencies were low during the early post-transplantation period. OLT patients with sustained viral responses had lower Treg frequencies than those with chronic hepatitis C, whereas Tr1 frequencies were significantly reduced in OLT patients with persistently normal alanine aminotransferase levels compared to those with chronic hepatitis C (p < 0.05). Treg frequencies positively correlated with HCV NS3 antigen-specific interferon-gamma responses, which corresponded to HCV clearance. Conclusions: Increased Treg frequencies and reduced HCV-NS3 antigen-specific responses recovered after viral eradication in post-OLT chronic hepatitis C patients. Reduced Tr1 frequencies were associated with hepatitis activity control, which may facilitate controlling chronic hepatitis C in patients after OLT. (C) 2014 Elsevier B.V. All rights reserved.
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