The immune reactivity role of HCV-induced liver infiltrating lymphocytes in hepatocellular damage

Yide Jin*, Laphalle Fuller, Manuel Carreno, Keith Zucker, David Roth, Violet Esquenazi, Theodore Karatzas, Sidney J. Swanson, Andreas G. Tzakis, Joshua Miller

*Corresponding author for this work

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Liver infiltrating lymphocytes (LIL) were isolated from HCV-positive (+) and HCV-negative (-) end-stage livers. Phenotypic analysis and functional studies using proliferative and lymphocytotoxic assays were performed with the isolated LIL. Two CD3+ lymphocyte populations were found in LIL using FITC anti-CD3 monoclonal antibodies (mAb). One was a bright fluorescence intensity population (as in PBL), and the other dim. We calculated the number of FITC-anti-CD3 mAbs bound per lymphocyte on PBL and LIL and found 80,040 ± 4628 and 39,615 ± 3932, respectively. Therefore, HCV+ and HCV- patient PBL contained approximately twice the number of CD3 molecules per cell than patient CD3+ LIL. LIL also contained approximately a threefold higher concentration of TCRαβ+, CD4-CD8-, and CD56,16 (NK) cells than the patient PBL. Thus, a major subset of LIL is phenotypically similar to mouse NK1.1+ 'intermediate' T cells. LIL freshly isolated from HCV+ livers exhibited weak CTL activity against EBV- or Con A-transformed lymphoblast targets infected with vaccinia-HCV recombinant virus (rHCV) or primary hepatocyte cultured cells. However, after in vitro coculture of LIL with rHCV, these cells developed a strong cytotoxicity for the above targets. In contrast, LIL from HCV- livers were not cytotoxic against the same targets. Histochemical studies (in situ) demonstrated that these hepatocytes express CD95, and stains demonstrated apoptosis. The HCV+ hepatocytes also express class I MHC molecules and ICAM-1. The addition of mAb specific for these adhesion molecules inhibited CML activity. Short-term cultured hepatocytes (targets) from HCV+ and HCV- patients produced low levels of cytokines IL-1β, IL-2, IL-6, TNFα, and IFN-γ but a high level of IL-8. It is speculated that LIL expressing reduced numbers of CD3 molecules may even function as immune regulators as proposed for intermediate T cells in mice.

Original languageEnglish (US)
Pages (from-to)140-153
Number of pages14
JournalJournal of Clinical Immunology
Volume17
Issue number2
DOIs
StatePublished - Apr 15 1997

Keywords

  • end-stage liver disease
  • hepatitis C virus
  • intermediate T cells
  • liver infiltrating lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Jin, Y., Fuller, L., Carreno, M., Zucker, K., Roth, D., Esquenazi, V., Karatzas, T., Swanson, S. J., Tzakis, A. G., & Miller, J. (1997). The immune reactivity role of HCV-induced liver infiltrating lymphocytes in hepatocellular damage. Journal of Clinical Immunology, 17(2), 140-153. https://doi.org/10.1023/A:1027326415164