Lack of optimal T-cell reactivity against the hepatitis C virus is associated with the development of fibrosis/cirrhosis during chronic hepatitis

Jayaprakash Sreenarasimhaiah, Andrés Jaramillo, Jeffrey Crippin, Mauricio Lisker-Melman, William C. Chapman, T. Mohanakumar

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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-γ enzyme-linked immunospot (ELISPOT) assay. The frequency of CD4+ Th1 and Th2 cells reactive to the HCV core antigen was determined by interferon-γ 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.

Original languageEnglish (US)
Pages (from-to)224-230
Number of pages7
JournalHuman Immunology
Volume64
Issue number2
DOIs
StatePublished - Feb 1 2003

Fingerprint

Chronic Hepatitis
Hepacivirus
Fibrosis
T-Lymphocytes
Histology
Chronic Hepatitis C
Virus Diseases
Enzyme-Linked Immunospot Assay
Inflammation
Interferons
Epitopes
Antigens
Th2 Cells
Th1 Cells
Interleukin-5
HLA Antigens
varespladib methyl

Keywords

  • CD4 T cells
  • CD8 T cells
  • Chronic infection
  • Cirrhosis
  • Hepatitis C virus

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Lack of optimal T-cell reactivity against the hepatitis C virus is associated with the development of fibrosis/cirrhosis during chronic hepatitis. / Sreenarasimhaiah, Jayaprakash; Jaramillo, Andrés; Crippin, Jeffrey; Lisker-Melman, Mauricio; Chapman, William C.; Mohanakumar, T.

In: Human Immunology, Vol. 64, No. 2, 01.02.2003, p. 224-230.

Research output: Contribution to journalArticle

Sreenarasimhaiah, Jayaprakash ; Jaramillo, Andrés ; Crippin, Jeffrey ; Lisker-Melman, Mauricio ; Chapman, William C. ; Mohanakumar, T. / Lack of optimal T-cell reactivity against the hepatitis C virus is associated with the development of fibrosis/cirrhosis during chronic hepatitis. In: Human Immunology. 2003 ; Vol. 64, No. 2. pp. 224-230.
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