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

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

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Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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