PMID- 12559624
OWN - NLM
STAT- MEDLINE
DCOM- 20030926
LR  - 20190906
IS  - 0198-8859 (Print)
IS  - 0198-8859 (Linking)
VI  - 64
IP  - 2
DP  - 2003 Feb
TI  - Lack of optimal T-cell reactivity against the hepatitis C virus is associated 
      with the development of fibrosis/cirrhosis during chronic hepatitis.
PG  - 224-30
AB  - Chronic hepatitis C virus (HCV) infection develops in 85% of exposed individuals 
      and 20% develop cirrhosis. However, the pathogenesis of this process is not 
      well-understood. The objective of this study was to determine whether 
      HCV-reactive T cells play a role in the process of development of cirrhosis 
      during chronic HCV infection. We analyzed 21 human leukocyte antigen (HLA)-A2 
      patients with chronic HCV infection (9 with histology of inflammation and 12 with 
      histology of fibrosis/cirrhosis). The frequency of CD8(+) T cells reactive to 12 
      HCV-derived epitopes was determined by an interferon-gamma enzyme-linked 
      immunospot (ELISPOT) assay. The frequency of CD4(+) Th1 and Th2 cells reactive to 
      the HCV core antigen was determined by interferon-gamma and interleukin-5 ELISPOT 
      assays, respectively. Patients with histology of inflammation showed a 
      significantly higher CD8(+) T-cell response to five HCV-derived epitopes 
      (YLLPRRGPRL [core], CINGVCWTV [NS3], LLCPAGHAV [NS3], ILAGYGAGV [NS4B], and 
      GLQDCTMLV [NS5B]) as compared with patients with histology of fibrosis/cirrhosis. 
      Also, patients with histology of inflammation showed a significantly higher 
      CD4(+) Th1 response to the HCV core antigen as compared to patients with 
      histology of fibrosis/cirrhosis. These results indicate that a lack of an optimal 
      T-cell response to HCV is associated with the development of cirrhosis during 
      chronic HCV infection.
FAU - Sreenarasimhaiah, Jayaprakash
AU  - Sreenarasimhaiah J
AD  - Department of Gastroenterology, Washington University School of Medicine, St. 
      Louis, Missouri 63110, USA.
FAU - Jaramillo, Andres
AU  - Jaramillo A
FAU - Crippin, Jeffrey
AU  - Crippin J
FAU - Lisker-Melman, Mauricio
AU  - Lisker-Melman M
FAU - Chapman, William C
AU  - Chapman WC
FAU - Mohanakumar, T
AU  - Mohanakumar T
LA  - eng
GR  - DK07130-27/DK/NIDDK NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Interleukin-5)
RN  - 0 (Peptide Fragments)
RN  - 0 (Viral Core Proteins)
RN  - 0 (Viral Matrix Proteins)
RN  - 0 (influenza matrix peptide (58-66))
RN  - 0 (nucleocapsid protein, Hepatitis C virus)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adult
MH  - Amino Acid Sequence
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Epitopes, T-Lymphocyte/immunology
MH  - Female
MH  - Genotype
MH  - HLA-A2 Antigen/analysis
MH  - Hepacivirus/*immunology
MH  - Hepatitis C, Chronic/complications/*immunology
MH  - Humans
MH  - Influenza A virus/immunology
MH  - Interferon-gamma/immunology
MH  - Interleukin-5/immunology
MH  - Liver/immunology/pathology
MH  - Liver Cirrhosis/etiology/*immunology
MH  - Male
MH  - Middle Aged
MH  - Mumps virus/immunology
MH  - Peptide Fragments/immunology
MH  - T-Lymphocyte Subsets/*immunology
MH  - Th1 Cells/immunology
MH  - Th2 Cells/immunology
MH  - Viral Core Proteins/immunology
MH  - Viral Matrix Proteins/immunology
EDAT- 2003/02/01 04:00
MHDA- 2003/09/27 05:00
CRDT- 2003/02/01 04:00
PHST- 2003/02/01 04:00 [pubmed]
PHST- 2003/09/27 05:00 [medline]
PHST- 2003/02/01 04:00 [entrez]
AID - S0198885902007814 [pii]
AID - 10.1016/s0198-8859(02)00781-4 [doi]
PST - ppublish
SO  - Hum Immunol. 2003 Feb;64(2):224-30. doi: 10.1016/s0198-8859(02)00781-4.