Premium
Cellular immunity to hepatitis C virus core protein and the response to interferon in patients with chronic hepatitis C
Author(s) -
Lasarte JuanJosé,
GarcíaGranero Marta,
López Ascensión,
Casares Noelia,
García Nicolás,
Civeira MaríaPilar,
BorrásCuesta Francisco,
Prieto Jesús
Publication year - 1998
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510280332
Subject(s) - medicine , immunology , interferon , peripheral blood mononuclear cell , hepatitis c virus , epitope , hepacivirus , antigen , hepatitis c , discontinuation , virology , alpha interferon , cellular immunity , virus , gastroenterology , biology , in vitro , biochemistry
To investigate the involvement of T‐cell response against hepatitis C virus (HCV) antigens in viral clearance after interferon therapy, we measured interleukin‐2 (IL‐2) production by peripheral mononuclear cells in response to HCV core in patients with chronic hepatitis C. In a cohort of 43 patients, we investigated the frequency of circulating core‐specific T‐helper (Th) cell precursors by the limiting‐dilution assay, and in a second cohort of 60 patients, we analyzed the response to specific core epitopes using 52 synthetic 15‐mer overlapping peptides. We observed that the frequency of core‐specific Th cell precursors was significantly higher in patients with sustained biochemical and virological response (SR) after interferon (IFN) therapy (median, 1/55,736) than in untreated patients (1/274,023) or that in patients who remained viremic after completion of the treatment—nonresponders (NR) plus transient responders (TR) (1/1,909,972). Patients who failed to respond to IFN (NR) and those who relapsed after IFN discontinuation (TR) had a similarly low number of precursors. The number of core peptides recognized by SR, TR, NR, UT, and healthy controls was 8.2 ± 1.5, 6.5 ± 1.2, 2.0 ± 0.5, 2.7 ± 0.9, and 0.3 ± 0.2, respectively. In SR, the intensity of the proliferative response to core peptides as estimated by the summation of stimulation indexes (ΣSI) was significantly higher than in NR and than in UT, but not different from that of TR. Our results indicate that both expansion of HCV‐specific Th cell precursors and Th cell recognition of multiple core epitopes seem to be important in the elimination of HCV after IFN therapy.