Premium
Cytotoxic capacity of hepatitis C virus (HCV)–specific lymphocytes after in vitro immunization with HCV‐derived lipopeptides
Author(s) -
Langhans Bettina,
Schweitzer Susann,
Braunschweiger Ingrid,
Schulz Monika,
Sauerbruch Tilman,
Spengler Ulrich
Publication year - 2005
Publication title -
cytometry part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.316
H-Index - 90
eISSN - 1552-4930
pISSN - 1552-4922
DOI - 10.1002/cyto.a.20136
Subject(s) - cytotoxic t cell , perforin , cytotoxicity , epitope , antigen , biology , hepatitis c virus , cd8 , virology , in vitro , microbiology and biotechnology , immunology , virus , biochemistry
Background Hepatitis C virus (HCV)–derived lipopeptides can induce epitope‐specific immune responses in lymphocytes from HCV‐naive individuals. We analyzed whether such T cells generated by in vitro immunization with HCV core‐derived lipopeptides exert HCV‐specific cytolytic activity. Methods Using a sensitive flow cytometric cytotoxicity assay we characterized HCV‐specific cytotoxicity in T cells generated in vitro with HCV core‐derived 25‐mer lipopeptides. In addition, we studied expressions of Fas ligand and perforin and interferon‐γ (IFN‐γ) secretion in HLA‐A2‐HCV core_35‐44 tetramer‐positive T cells generated with lipopeptide amino acid 20‐44 (LP20‐44). Results CD8 + T cells induced in vitro with HCV core‐derived lipopeptides only infrequently exerted HCV‐specific cytotoxicity, irrespective of whether antigen‐coated T2 cells or autologous B lymphoblasts were used as targets. Detailed analysis of HLA‐A2‐HCV core_35‐44 tetramer‐positive T cells generated with LP20‐44 revealed that in vitro immunization resulted in T cells that secreted IFN‐γ after antigen‐specific restimulation and that upregulated expression of Fas ligand but not of perforin. Conclusions Our data confirm at the functional level that HCV lipopeptides induce antigen‐specific T lymphocytes that produce IFN‐γ but exert significant cytotoxicity in only a minority of experiments, probably because expression of cytolytic effector molecules is not enhanced in their granules. © 2005 Wiley‐Liss, Inc.