CD161+CD4+ T cells are enriched in the liver during chronic hepatitis and associated with co-secretion of IL-22 and IFN-γ

Yu Hoi Kang, Bianca Seigel, Bertram Bengsch, Vicki M. Fleming, Eva K. Billerbeck, Ruth Simmons, Lucy Walker, Chris B. Willberg, Eleanor J. Barnes, Anisha Bhagwanani, Ye H. Oo, Hubert E. Blum, David H. Adams, Robert Thimme, Paul Klenerman

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Hepatitis C virus infection is a major cause of chronic liver disease. CD4+ T cells play a key role in disease outcome. However, the critical functions and associated phenotypes of intrahepatic CD4+ T cells are not well defined. We have previously shown that CD8+T cells expressing the C type lectin CD161 are highly enriched in the human liver, especially during chronic hepatitis. These cells are associated with a type 17 differentiation pattern and express cytokines including IL-17A, IL-22, and IFN-γ. We therefore analyzed expression of CD161 on CD4+ T cells in blood and liver and addressed the relevant phenotype and functional capacity of these populations. We observed marked enrichmentof CD161+ CD4+ T cells in the liver during chronic hepatitis such that they are the dominant subtype (mean 55% of CD4+ T cells). IL-22 and IL-17 secreting CD4+ T cells were readily found in the livers of HCV and NASH donors, although not enriched compared to blood. There was, however, specific enrichment of a novel subset of IL-22/IFN-γ dual secretors (p = 0.02) compared to blood, a res+ult reconfirmed with direct ex vivo analyses. These data indicate the dominance of CD161+ expressing lymphocyte populations within the hepatic infiltrate, associated with a distinct cytokine profile. Given their documented roles as antiviral and hepatoprotective cytokines respectively, the impact of co-secretion of IFN-γ and IL-22 in the liver may be particularly significant.

Original languageEnglish (US)
Article numberArticle 346
JournalFrontiers in Immunology
Volume3
Issue numberNOV
DOIs
StatePublished - Dec 1 2012
Externally publishedYes

Fingerprint

Chronic Hepatitis
T-Lymphocytes
Liver
Interleukin-17
Cytokines
C-Type Lectins
Phenotype
Virus Diseases
interleukin-22
Hepacivirus
Population
Antiviral Agents
Liver Diseases
Chronic Disease
Lymphocytes

Keywords

  • CD161
  • CD4 t cell
  • HCV
  • Hepatic inflammation
  • IL-22

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

CD161+CD4+ T cells are enriched in the liver during chronic hepatitis and associated with co-secretion of IL-22 and IFN-γ . / Kang, Yu Hoi; Seigel, Bianca; Bengsch, Bertram; Fleming, Vicki M.; Billerbeck, Eva K.; Simmons, Ruth; Walker, Lucy; Willberg, Chris B.; Barnes, Eleanor J.; Bhagwanani, Anisha; Oo, Ye H.; Blum, Hubert E.; Adams, David H.; Thimme, Robert; Klenerman, Paul.

In: Frontiers in Immunology, Vol. 3, No. NOV, Article 346, 01.12.2012.

Research output: Contribution to journalArticle

Kang, YH, Seigel, B, Bengsch, B, Fleming, VM, Billerbeck, EK, Simmons, R, Walker, L, Willberg, CB, Barnes, EJ, Bhagwanani, A, Oo, YH, Blum, HE, Adams, DH, Thimme, R & Klenerman, P 2012, 'CD161+CD4+ T cells are enriched in the liver during chronic hepatitis and associated with co-secretion of IL-22 and IFN-γ ', Frontiers in Immunology, vol. 3, no. NOV, Article 346. https://doi.org/10.3389/fimmu.2012.00346
Kang, Yu Hoi ; Seigel, Bianca ; Bengsch, Bertram ; Fleming, Vicki M. ; Billerbeck, Eva K. ; Simmons, Ruth ; Walker, Lucy ; Willberg, Chris B. ; Barnes, Eleanor J. ; Bhagwanani, Anisha ; Oo, Ye H. ; Blum, Hubert E. ; Adams, David H. ; Thimme, Robert ; Klenerman, Paul. / CD161+CD4+ T cells are enriched in the liver during chronic hepatitis and associated with co-secretion of IL-22 and IFN-γ In: Frontiers in Immunology. 2012 ; Vol. 3, No. NOV.
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AU - Seigel, Bianca

AU - Bengsch, Bertram

AU - Fleming, Vicki M.

AU - Billerbeck, Eva K.

AU - Simmons, Ruth

AU - Walker, Lucy

AU - Willberg, Chris B.

AU - Barnes, Eleanor J.

AU - Bhagwanani, Anisha

AU - Oo, Ye H.

AU - Blum, Hubert E.

AU - Adams, David H.

AU - Thimme, Robert

AU - Klenerman, Paul

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AB - Hepatitis C virus infection is a major cause of chronic liver disease. CD4+ T cells play a key role in disease outcome. However, the critical functions and associated phenotypes of intrahepatic CD4+ T cells are not well defined. We have previously shown that CD8+T cells expressing the C type lectin CD161 are highly enriched in the human liver, especially during chronic hepatitis. These cells are associated with a type 17 differentiation pattern and express cytokines including IL-17A, IL-22, and IFN-γ. We therefore analyzed expression of CD161 on CD4+ T cells in blood and liver and addressed the relevant phenotype and functional capacity of these populations. We observed marked enrichmentof CD161+ CD4+ T cells in the liver during chronic hepatitis such that they are the dominant subtype (mean 55% of CD4+ T cells). IL-22 and IL-17 secreting CD4+ T cells were readily found in the livers of HCV and NASH donors, although not enriched compared to blood. There was, however, specific enrichment of a novel subset of IL-22/IFN-γ dual secretors (p = 0.02) compared to blood, a res+ult reconfirmed with direct ex vivo analyses. These data indicate the dominance of CD161+ expressing lymphocyte populations within the hepatic infiltrate, associated with a distinct cytokine profile. Given their documented roles as antiviral and hepatoprotective cytokines respectively, the impact of co-secretion of IFN-γ and IL-22 in the liver may be particularly significant.

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