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Liver-infiltrating and circulating CD4+ T cells in chronic hepatitis C: immunodominant epitopes, HLA-restriction and functional significance (from Liver 1996, 16, 174-182)
Bibliografi
Author:
Lohr, Hanns F.
;
Schlaak, Jorg F.
;
Kolmannsperger, Stefan
;
Dienes, Hans-Peter
;
Buschenfelde, Karl-Hermann Meyer zum
;
Gerken, Guido
Topik:
Chronic hepatitis C
;
Cytokine release
;
HCV-specific T cells
;
Liver-infiltrating T cells
;
Th1 helper cells
;
Validation ref - 6
Bahasa:
(EN )
Penerbit:
Munksgaard
Tahun Terbit:
1996
Jenis:
Article - diterbitkan di jurnal ilmiah internasional
Fulltext:
lhr2008.pdf
(1.18MB;
0 download
)
Abstract
The aim was to assess the specificity and functional significance of liver-infiltrating and peripheral blood T cells in chronic hepatitis C. Peripheral blood mononuclear cells hepatitis C virus from 50 of 58 (86.2%) patients with chronic hepatitis C virus infection and 6 of 28 (21.4%) controls showed a proliferative T cell response to at least one of 16 synthetic peptides covering highly conserved regions of the core, envelope (El) and non-structural regions (NS4) of hepatitis C virus. However, six immunodominant peptides were exclusively recognized by the proliferating blood mononuclear cells from 46 patients with chronic hepatitis C virus infection (79.3%). Fine specificity and HLA-restriction were studied with 15 peptide-specific CD4' T cell lines and 23 T cell clones isolated from liver tissue and peripheral blood of 12 patients with chronic hepatitis C. It was demonstrated that the peptide-specific response of CD4' T cells was restricted to the presence of autologous accessory cells and HLA-DR and -DP molecules. Eight peptide-specific T cell lines and five T cell clones derived from liver tissue and peripheral blood, released interferon-y (200-6600 pg/ml) and tumor necrosis factor-a ( 100400 pg/ml) and no or little interleukin-4 (<140 pg/ml) after peptide-specific or mitogeneic stimulation, thus resembling a Thl-like cytokine profile. Patients with active liver disease showed significantly higher proliferative responses to hepatitis C virus core peptides than asymptomatic hepatitis C virus carriers or complete responders to interferon therapy. In conclusion, class 11-restricted CD4' T cell responses to some immunodominant epitopes within the hepatitis core region correlated with disease activity in chronic hepatitis C virus infection. Functionally, liver-infiltrating and peripheral blood T cells released Th 1 -like cytokines in response to the specific stimulus. Thus, it can be suggested that CD4' T cells can mediate the pathogenesis of chronic hepatitis C virus induced liver disease.
[validation ref - 6]
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