Premium
Intrahepatic and circulating HLA class II–restricted, hepatitis C virus–specific T cells: Functional characterization in patients with chronic hepatitis C
Author(s) -
Penna Amalia,
Missale Gabriele,
Lamonaca Vincenzo,
Pilli Massimo,
Mori Cristina,
Zanelli Paola,
Cavalli Albertina,
Elia Gianfranco,
Ferrari Carlo
Publication year - 2002
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2002.33153
Subject(s) - epitope , hepatitis c virus , immunology , antigen , biology , virology , virus , major histocompatibility complex , t cell receptor , t cell , medicine , immune system
To compare the functional features of circulating and intrahepatic hepatitis C virus (HCV)‐specific CD4+ T cells in chronic HCV infection, peripheral blood and liver‐infiltrating lymphocytes from 29 patients with chronic hepatitis C were stimulated with structural and nonstructural HCV proteins to produce antigen‐specific T‐cell lines and clones. Antigen specificity, fine specificity, phenotype, cytokine production, and T‐cell receptor (TCR)‐vβ chain expression were analyzed. The results indicate a hierarchy of stimulatory capacity by the different HCV proteins, core being the antigen most frequently recognized by CD4+ intrahepatic lymphocytes, followed by NS4 and NS5. The CD4 response was directed simultaneously against different HCV proteins in individual patients, but fine‐specificity analysis indicated that the response was generally focused on a limited number of immunodominant epitopes. Although the narrowly focused nature of this response may favor the emergence of escape mutations, this event was not observed by following‐up over time the sequence of 2 epitopes strongly immunodominant for intrahepatic CD4 cells of a patient with chronic HCV infection. In conclusion, simultaneous analysis of peripheral blood and intrahepatic CD4 cells in the same patients indicated a predominant Th1 profile of HCV‐specific CD4 cells and suggests a specific compartmentalization of virus‐specific T cells into the liver.