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

35 Citations (Scopus)

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

Fingerprint

Lymphocytes
Liver
Hepatocytes
Fluorescein-5-isothiocyanate
Monoclonal Antibodies
T-Lymphocytes
Vaccinia
Intercellular Adhesion Molecule-1
Coculture Techniques
Human Herpesvirus 4
Interleukin-8
Interleukin-1
Natural Killer Cells
Population
Interleukin-2
Cultured Cells
Interleukin-6
Coloring Agents
Fluorescence
Apoptosis

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

The immune reactivity role of HCV-induced liver infiltrating lymphocytes in hepatocellular damage. / Jin, Yide; Fuller, Laphalle; Carreno, Manuel; Zucker, Keith; Roth, David; Esquenazi, Violet; Karatzas, Theodore; Swanson, Sidney J.; Tzakis, Andreas G.; Miller, Joshua.

In: Journal of Clinical Immunology, Vol. 17, No. 2, 15.04.1997, p. 140-153.

Research output: Contribution to journalArticle

Jin, Y, Fuller, L, Carreno, M, Zucker, K, Roth, D, Esquenazi, V, Karatzas, T, Swanson, SJ, Tzakis, AG & Miller, J 1997, 'The immune reactivity role of HCV-induced liver infiltrating lymphocytes in hepatocellular damage', Journal of Clinical Immunology, vol. 17, no. 2, pp. 140-153. https://doi.org/10.1023/A:1027326415164
Jin, Yide ; Fuller, Laphalle ; Carreno, Manuel ; Zucker, Keith ; Roth, David ; Esquenazi, Violet ; Karatzas, Theodore ; Swanson, Sidney J. ; Tzakis, Andreas G. ; Miller, Joshua. / The immune reactivity role of HCV-induced liver infiltrating lymphocytes in hepatocellular damage. In: Journal of Clinical Immunology. 1997 ; Vol. 17, No. 2. pp. 140-153.
@article{c13d09f7a0a64cd79f3e8ca56c57cc23,
title = "The immune reactivity role of HCV-induced liver infiltrating lymphocytes in hepatocellular damage",
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.",
keywords = "end-stage liver disease, hepatitis C virus, intermediate T cells, liver infiltrating lymphocytes",
author = "Yide Jin and Laphalle Fuller and Manuel Carreno and Keith Zucker and David Roth and Violet Esquenazi and Theodore Karatzas and Swanson, {Sidney J.} and Tzakis, {Andreas G.} and Joshua Miller",
year = "1997",
month = "4",
day = "15",
doi = "10.1023/A:1027326415164",
language = "English",
volume = "17",
pages = "140--153",
journal = "Journal of Clinical Immunology",
issn = "0271-9142",
publisher = "Springer New York",
number = "2",

}

TY - JOUR

T1 - The immune reactivity role of HCV-induced liver infiltrating lymphocytes in hepatocellular damage

AU - Jin, Yide

AU - Fuller, Laphalle

AU - Carreno, Manuel

AU - Zucker, Keith

AU - Roth, David

AU - Esquenazi, Violet

AU - Karatzas, Theodore

AU - Swanson, Sidney J.

AU - Tzakis, Andreas G.

AU - Miller, Joshua

PY - 1997/4/15

Y1 - 1997/4/15

N2 - 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.

AB - 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.

KW - end-stage liver disease

KW - hepatitis C virus

KW - intermediate T cells

KW - liver infiltrating lymphocytes

UR - http://www.scopus.com/inward/record.url?scp=8244239686&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=8244239686&partnerID=8YFLogxK

U2 - 10.1023/A:1027326415164

DO - 10.1023/A:1027326415164

M3 - Article

C2 - 9083890

AN - SCOPUS:8244239686

VL - 17

SP - 140

EP - 153

JO - Journal of Clinical Immunology

JF - Journal of Clinical Immunology

SN - 0271-9142

IS - 2

ER -