CD1 expression and CD1-restricted T cell activity in normal and tumour-bearing human liver

Tony Kenna, Margaret O'Brien, Andrew E. Hogan, Mark A. Exley, Steven A. Porcelli, John E. Hegarty, Cliona O'Farrelly, Derek G. Doherty

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

CD1d-restricted natural killer T (NKT) cells expressing invariant Vα14Jα18 T cell receptor α-chains are abundant in murine liver and are implicated in the control of malignancy, infection and autoimmunity. Invariant NKT cells have potent anti-metastatic effects in mice and phase I clinical trials involving their homologues in humans are ongoing. However, invariant NKT cells are less abundant in human liver (∼0.5% of hepatic T cells) than in murine liver (up to 50%) and it is not known if other hepatic T cells are CD1-restricted. We have examined expression of CD1a, CD1b, CD1c and CD1d mRNA and protein in human liver and evaluated the reactivity of mononuclear cells (MNC) from histologically normal and tumour-bearing human liver specimens against these CD1 isoforms. Messenger RNA for all CD1 isotypes was detectable in all liver samples. CD1c and CD1d were expressed at the protein level by hepatic MNC. CD1d, only, was detectable at the cell surface, but CD1c and CD1d were found at an intracellular location in significant numbers of liver MNC. CD1b was not expressed by MNC from healthy livers but was detectable within MNC in all tumour samples tested. Hepatic T cells exhibited reactivity against C1R cells expressing transfected CD1c and CD1d, but neither CD1a nor CD1b. These cells secreted interferon-γ (IFN-γ) but not interleukin-4 (IL-4) upon stimulation. In contrast, similar numbers of peripheral T cells released 13- and 16-fold less IFN-γ in response to CD1c and CD1d, respectively. CD1c and CD1d expression and T cell reactivity were not altered in tumour-bearing liver specimens compared to histologically normal livers. These data suggest that, in addition to invariant CD1d-restricted NKT cells, autoreactive T cells that recognise CD1c and CD1d and release inflammatory cytokines are abundant in human liver.

Original languageEnglish (US)
Pages (from-to)563-572
Number of pages10
JournalCancer Immunology, Immunotherapy
Volume56
Issue number4
DOIs
StatePublished - Apr 2007

Fingerprint

T-Lymphocytes
Liver
Natural Killer T-Cells
Neoplasms
Hepatocytes
Interferons
Messenger RNA
Clinical Trials, Phase I
Infection Control
T-Cell Antigen Receptor
Autoimmunity
Interleukin-4
Protein Isoforms
Proteins
Cytokines

Keywords

  • Human
  • Liver
  • Natural killer T cells
  • T cells
  • Tumour immunity

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Oncology

Cite this

CD1 expression and CD1-restricted T cell activity in normal and tumour-bearing human liver. / Kenna, Tony; O'Brien, Margaret; Hogan, Andrew E.; Exley, Mark A.; Porcelli, Steven A.; Hegarty, John E.; O'Farrelly, Cliona; Doherty, Derek G.

In: Cancer Immunology, Immunotherapy, Vol. 56, No. 4, 04.2007, p. 563-572.

Research output: Contribution to journalArticle

Kenna, T, O'Brien, M, Hogan, AE, Exley, MA, Porcelli, SA, Hegarty, JE, O'Farrelly, C & Doherty, DG 2007, 'CD1 expression and CD1-restricted T cell activity in normal and tumour-bearing human liver', Cancer Immunology, Immunotherapy, vol. 56, no. 4, pp. 563-572. https://doi.org/10.1007/s00262-006-0215-x
Kenna, Tony ; O'Brien, Margaret ; Hogan, Andrew E. ; Exley, Mark A. ; Porcelli, Steven A. ; Hegarty, John E. ; O'Farrelly, Cliona ; Doherty, Derek G. / CD1 expression and CD1-restricted T cell activity in normal and tumour-bearing human liver. In: Cancer Immunology, Immunotherapy. 2007 ; Vol. 56, No. 4. pp. 563-572.
@article{fd9a43bbd4474d54b170f75b16cd4a15,
title = "CD1 expression and CD1-restricted T cell activity in normal and tumour-bearing human liver",
abstract = "CD1d-restricted natural killer T (NKT) cells expressing invariant Vα14Jα18 T cell receptor α-chains are abundant in murine liver and are implicated in the control of malignancy, infection and autoimmunity. Invariant NKT cells have potent anti-metastatic effects in mice and phase I clinical trials involving their homologues in humans are ongoing. However, invariant NKT cells are less abundant in human liver (∼0.5{\%} of hepatic T cells) than in murine liver (up to 50{\%}) and it is not known if other hepatic T cells are CD1-restricted. We have examined expression of CD1a, CD1b, CD1c and CD1d mRNA and protein in human liver and evaluated the reactivity of mononuclear cells (MNC) from histologically normal and tumour-bearing human liver specimens against these CD1 isoforms. Messenger RNA for all CD1 isotypes was detectable in all liver samples. CD1c and CD1d were expressed at the protein level by hepatic MNC. CD1d, only, was detectable at the cell surface, but CD1c and CD1d were found at an intracellular location in significant numbers of liver MNC. CD1b was not expressed by MNC from healthy livers but was detectable within MNC in all tumour samples tested. Hepatic T cells exhibited reactivity against C1R cells expressing transfected CD1c and CD1d, but neither CD1a nor CD1b. These cells secreted interferon-γ (IFN-γ) but not interleukin-4 (IL-4) upon stimulation. In contrast, similar numbers of peripheral T cells released 13- and 16-fold less IFN-γ in response to CD1c and CD1d, respectively. CD1c and CD1d expression and T cell reactivity were not altered in tumour-bearing liver specimens compared to histologically normal livers. These data suggest that, in addition to invariant CD1d-restricted NKT cells, autoreactive T cells that recognise CD1c and CD1d and release inflammatory cytokines are abundant in human liver.",
keywords = "Human, Liver, Natural killer T cells, T cells, Tumour immunity",
author = "Tony Kenna and Margaret O'Brien and Hogan, {Andrew E.} and Exley, {Mark A.} and Porcelli, {Steven A.} and Hegarty, {John E.} and Cliona O'Farrelly and Doherty, {Derek G.}",
year = "2007",
month = "4",
doi = "10.1007/s00262-006-0215-x",
language = "English (US)",
volume = "56",
pages = "563--572",
journal = "Medical Oncology and Tumor Pharmacotherapy",
issn = "0340-7004",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "4",

}

TY - JOUR

T1 - CD1 expression and CD1-restricted T cell activity in normal and tumour-bearing human liver

AU - Kenna, Tony

AU - O'Brien, Margaret

AU - Hogan, Andrew E.

AU - Exley, Mark A.

AU - Porcelli, Steven A.

AU - Hegarty, John E.

AU - O'Farrelly, Cliona

AU - Doherty, Derek G.

PY - 2007/4

Y1 - 2007/4

N2 - CD1d-restricted natural killer T (NKT) cells expressing invariant Vα14Jα18 T cell receptor α-chains are abundant in murine liver and are implicated in the control of malignancy, infection and autoimmunity. Invariant NKT cells have potent anti-metastatic effects in mice and phase I clinical trials involving their homologues in humans are ongoing. However, invariant NKT cells are less abundant in human liver (∼0.5% of hepatic T cells) than in murine liver (up to 50%) and it is not known if other hepatic T cells are CD1-restricted. We have examined expression of CD1a, CD1b, CD1c and CD1d mRNA and protein in human liver and evaluated the reactivity of mononuclear cells (MNC) from histologically normal and tumour-bearing human liver specimens against these CD1 isoforms. Messenger RNA for all CD1 isotypes was detectable in all liver samples. CD1c and CD1d were expressed at the protein level by hepatic MNC. CD1d, only, was detectable at the cell surface, but CD1c and CD1d were found at an intracellular location in significant numbers of liver MNC. CD1b was not expressed by MNC from healthy livers but was detectable within MNC in all tumour samples tested. Hepatic T cells exhibited reactivity against C1R cells expressing transfected CD1c and CD1d, but neither CD1a nor CD1b. These cells secreted interferon-γ (IFN-γ) but not interleukin-4 (IL-4) upon stimulation. In contrast, similar numbers of peripheral T cells released 13- and 16-fold less IFN-γ in response to CD1c and CD1d, respectively. CD1c and CD1d expression and T cell reactivity were not altered in tumour-bearing liver specimens compared to histologically normal livers. These data suggest that, in addition to invariant CD1d-restricted NKT cells, autoreactive T cells that recognise CD1c and CD1d and release inflammatory cytokines are abundant in human liver.

AB - CD1d-restricted natural killer T (NKT) cells expressing invariant Vα14Jα18 T cell receptor α-chains are abundant in murine liver and are implicated in the control of malignancy, infection and autoimmunity. Invariant NKT cells have potent anti-metastatic effects in mice and phase I clinical trials involving their homologues in humans are ongoing. However, invariant NKT cells are less abundant in human liver (∼0.5% of hepatic T cells) than in murine liver (up to 50%) and it is not known if other hepatic T cells are CD1-restricted. We have examined expression of CD1a, CD1b, CD1c and CD1d mRNA and protein in human liver and evaluated the reactivity of mononuclear cells (MNC) from histologically normal and tumour-bearing human liver specimens against these CD1 isoforms. Messenger RNA for all CD1 isotypes was detectable in all liver samples. CD1c and CD1d were expressed at the protein level by hepatic MNC. CD1d, only, was detectable at the cell surface, but CD1c and CD1d were found at an intracellular location in significant numbers of liver MNC. CD1b was not expressed by MNC from healthy livers but was detectable within MNC in all tumour samples tested. Hepatic T cells exhibited reactivity against C1R cells expressing transfected CD1c and CD1d, but neither CD1a nor CD1b. These cells secreted interferon-γ (IFN-γ) but not interleukin-4 (IL-4) upon stimulation. In contrast, similar numbers of peripheral T cells released 13- and 16-fold less IFN-γ in response to CD1c and CD1d, respectively. CD1c and CD1d expression and T cell reactivity were not altered in tumour-bearing liver specimens compared to histologically normal livers. These data suggest that, in addition to invariant CD1d-restricted NKT cells, autoreactive T cells that recognise CD1c and CD1d and release inflammatory cytokines are abundant in human liver.

KW - Human

KW - Liver

KW - Natural killer T cells

KW - T cells

KW - Tumour immunity

UR - http://www.scopus.com/inward/record.url?scp=33846798498&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846798498&partnerID=8YFLogxK

U2 - 10.1007/s00262-006-0215-x

DO - 10.1007/s00262-006-0215-x

M3 - Article

C2 - 16924493

AN - SCOPUS:33846798498

VL - 56

SP - 563

EP - 572

JO - Medical Oncology and Tumor Pharmacotherapy

JF - Medical Oncology and Tumor Pharmacotherapy

SN - 0340-7004

IS - 4

ER -