Effector CD8+ T cell-derived interleukin-10 enhances acute liver immunopathology

J Fioravanti, P Di Lucia, D Magini, F Moalli, C Boni, AP Benechet, V Fumagalli, D Inverso, A Vecchi, A Fiocchi, S Wieland, R Purcell, C Ferrari, FV Chisari, LG Guidotti, M Iannacone

Research output: Contribution to journalArticle

Abstract

BACKGROUND & AIMS: Besides secreting pro-inflammatory cytokines, chemokines and effector molecules, effector CD8+ T cells that arise upon acute infection with certain viruses have been shown to produce the regulatory cytokine interleukin (IL)-10 and, therefore, contain immunopathology. Whether the same occurs during acute hepatitis B virus (HBV) infection and role that IL-10 might play in liver disease is currently unknown. METHODS: Mouse models of acute HBV pathogenesis, as well as chimpanzees and patients acutely infected with HBV, were used to analyse the role of CD8+ T cell-derived IL-10 in liver immunopathology. RESULTS: Mouse HBV-specific effector CD8+ T cells produce significant amounts of IL-10 upon in vivo antigen encounter. This is corroborated by longitudinal data in a chimpanzee acutely infected with HBV, where serum IL-10 was readily detectable and correlated with intrahepatic CD8+ T cell infiltration and liver disease severity. Unexpectedly, mouse and human CD8+ T cell-derived IL-10 was found to act in an autocrine/paracrine fashion to enhance IL-2 responsiveness, thus preventing antigen-induced HBV-specific effector CD8+ T cell apoptosis. Accordingly, the use of mouse models of HBV pathogenesis revealed that the IL-10 produced by effector CD8+ T cells promoted their own intrahepatic survival and, thus supported, rather than suppressed liver immunopathology. CONCLUSION: Effector CD8+ T cell-derived IL-10 enhances acute liver immunopathology. Altogether, these results extend our understanding of the cell- and tissue-specific role that IL-10 exerts in immune regulation. Lay summary: Interleukin-10 is mostly regarded as an immunosuppressive cytokine. We show here that HBV-specific CD8+ T cells produce IL-10 upon antigen recognition and that this cytokine enhances CD8+ T cell survival. As such, IL-10 paradoxically promotes rather than suppresses liver disease. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Original languageEnglish
Pages (from-to)543-548
Number of pages6
JournalJournal of Hepatology
Volume67
Issue number3
DOIs
Publication statusPublished - 2017

Fingerprint

Interleukin-10
T-Lymphocytes
Hepatitis B virus
Liver
Cytokines
Liver Diseases
Pan troglodytes
Antigens
Murine hepatitis virus
Virus Diseases
Immunosuppressive Agents
Chemokines
Interleukin-2
Cell Survival
Apoptosis
Viruses
Survival

Cite this

Effector CD8+ T cell-derived interleukin-10 enhances acute liver immunopathology. / Fioravanti, J; Di Lucia, P; Magini, D; Moalli, F; Boni, C; Benechet, AP; Fumagalli, V; Inverso, D; Vecchi, A; Fiocchi, A; Wieland, S; Purcell, R; Ferrari, C; Chisari, FV; Guidotti, LG; Iannacone, M.

In: Journal of Hepatology, Vol. 67, No. 3, 2017, p. 543-548.

Research output: Contribution to journalArticle

Fioravanti, J, Di Lucia, P, Magini, D, Moalli, F, Boni, C, Benechet, AP, Fumagalli, V, Inverso, D, Vecchi, A, Fiocchi, A, Wieland, S, Purcell, R, Ferrari, C, Chisari, FV, Guidotti, LG & Iannacone, M 2017, 'Effector CD8+ T cell-derived interleukin-10 enhances acute liver immunopathology', Journal of Hepatology, vol. 67, no. 3, pp. 543-548. https://doi.org/10.1016/j.jhep.2017.04.020
Fioravanti, J ; Di Lucia, P ; Magini, D ; Moalli, F ; Boni, C ; Benechet, AP ; Fumagalli, V ; Inverso, D ; Vecchi, A ; Fiocchi, A ; Wieland, S ; Purcell, R ; Ferrari, C ; Chisari, FV ; Guidotti, LG ; Iannacone, M. / Effector CD8+ T cell-derived interleukin-10 enhances acute liver immunopathology. In: Journal of Hepatology. 2017 ; Vol. 67, No. 3. pp. 543-548.
@article{fe242a04b1ae4baab7733943467d1dd3,
title = "Effector CD8+ T cell-derived interleukin-10 enhances acute liver immunopathology",
abstract = "BACKGROUND & AIMS: Besides secreting pro-inflammatory cytokines, chemokines and effector molecules, effector CD8+ T cells that arise upon acute infection with certain viruses have been shown to produce the regulatory cytokine interleukin (IL)-10 and, therefore, contain immunopathology. Whether the same occurs during acute hepatitis B virus (HBV) infection and role that IL-10 might play in liver disease is currently unknown. METHODS: Mouse models of acute HBV pathogenesis, as well as chimpanzees and patients acutely infected with HBV, were used to analyse the role of CD8+ T cell-derived IL-10 in liver immunopathology. RESULTS: Mouse HBV-specific effector CD8+ T cells produce significant amounts of IL-10 upon in vivo antigen encounter. This is corroborated by longitudinal data in a chimpanzee acutely infected with HBV, where serum IL-10 was readily detectable and correlated with intrahepatic CD8+ T cell infiltration and liver disease severity. Unexpectedly, mouse and human CD8+ T cell-derived IL-10 was found to act in an autocrine/paracrine fashion to enhance IL-2 responsiveness, thus preventing antigen-induced HBV-specific effector CD8+ T cell apoptosis. Accordingly, the use of mouse models of HBV pathogenesis revealed that the IL-10 produced by effector CD8+ T cells promoted their own intrahepatic survival and, thus supported, rather than suppressed liver immunopathology. CONCLUSION: Effector CD8+ T cell-derived IL-10 enhances acute liver immunopathology. Altogether, these results extend our understanding of the cell- and tissue-specific role that IL-10 exerts in immune regulation. Lay summary: Interleukin-10 is mostly regarded as an immunosuppressive cytokine. We show here that HBV-specific CD8+ T cells produce IL-10 upon antigen recognition and that this cytokine enhances CD8+ T cell survival. As such, IL-10 paradoxically promotes rather than suppresses liver disease. Copyright {\circledC} 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.",
author = "J Fioravanti and {Di Lucia}, P and D Magini and F Moalli and C Boni and AP Benechet and V Fumagalli and D Inverso and A Vecchi and A Fiocchi and S Wieland and R Purcell and C Ferrari and FV Chisari and LG Guidotti and M Iannacone",
year = "2017",
doi = "10.1016/j.jhep.2017.04.020",
language = "English",
volume = "67",
pages = "543--548",
journal = "Journal of Hepatology",
issn = "0168-8278",
publisher = "Elsevier B.V.",
number = "3",

}

TY - JOUR

T1 - Effector CD8+ T cell-derived interleukin-10 enhances acute liver immunopathology

AU - Fioravanti, J

AU - Di Lucia, P

AU - Magini, D

AU - Moalli, F

AU - Boni, C

AU - Benechet, AP

AU - Fumagalli, V

AU - Inverso, D

AU - Vecchi, A

AU - Fiocchi, A

AU - Wieland, S

AU - Purcell, R

AU - Ferrari, C

AU - Chisari, FV

AU - Guidotti, LG

AU - Iannacone, M

PY - 2017

Y1 - 2017

N2 - BACKGROUND & AIMS: Besides secreting pro-inflammatory cytokines, chemokines and effector molecules, effector CD8+ T cells that arise upon acute infection with certain viruses have been shown to produce the regulatory cytokine interleukin (IL)-10 and, therefore, contain immunopathology. Whether the same occurs during acute hepatitis B virus (HBV) infection and role that IL-10 might play in liver disease is currently unknown. METHODS: Mouse models of acute HBV pathogenesis, as well as chimpanzees and patients acutely infected with HBV, were used to analyse the role of CD8+ T cell-derived IL-10 in liver immunopathology. RESULTS: Mouse HBV-specific effector CD8+ T cells produce significant amounts of IL-10 upon in vivo antigen encounter. This is corroborated by longitudinal data in a chimpanzee acutely infected with HBV, where serum IL-10 was readily detectable and correlated with intrahepatic CD8+ T cell infiltration and liver disease severity. Unexpectedly, mouse and human CD8+ T cell-derived IL-10 was found to act in an autocrine/paracrine fashion to enhance IL-2 responsiveness, thus preventing antigen-induced HBV-specific effector CD8+ T cell apoptosis. Accordingly, the use of mouse models of HBV pathogenesis revealed that the IL-10 produced by effector CD8+ T cells promoted their own intrahepatic survival and, thus supported, rather than suppressed liver immunopathology. CONCLUSION: Effector CD8+ T cell-derived IL-10 enhances acute liver immunopathology. Altogether, these results extend our understanding of the cell- and tissue-specific role that IL-10 exerts in immune regulation. Lay summary: Interleukin-10 is mostly regarded as an immunosuppressive cytokine. We show here that HBV-specific CD8+ T cells produce IL-10 upon antigen recognition and that this cytokine enhances CD8+ T cell survival. As such, IL-10 paradoxically promotes rather than suppresses liver disease. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

AB - BACKGROUND & AIMS: Besides secreting pro-inflammatory cytokines, chemokines and effector molecules, effector CD8+ T cells that arise upon acute infection with certain viruses have been shown to produce the regulatory cytokine interleukin (IL)-10 and, therefore, contain immunopathology. Whether the same occurs during acute hepatitis B virus (HBV) infection and role that IL-10 might play in liver disease is currently unknown. METHODS: Mouse models of acute HBV pathogenesis, as well as chimpanzees and patients acutely infected with HBV, were used to analyse the role of CD8+ T cell-derived IL-10 in liver immunopathology. RESULTS: Mouse HBV-specific effector CD8+ T cells produce significant amounts of IL-10 upon in vivo antigen encounter. This is corroborated by longitudinal data in a chimpanzee acutely infected with HBV, where serum IL-10 was readily detectable and correlated with intrahepatic CD8+ T cell infiltration and liver disease severity. Unexpectedly, mouse and human CD8+ T cell-derived IL-10 was found to act in an autocrine/paracrine fashion to enhance IL-2 responsiveness, thus preventing antigen-induced HBV-specific effector CD8+ T cell apoptosis. Accordingly, the use of mouse models of HBV pathogenesis revealed that the IL-10 produced by effector CD8+ T cells promoted their own intrahepatic survival and, thus supported, rather than suppressed liver immunopathology. CONCLUSION: Effector CD8+ T cell-derived IL-10 enhances acute liver immunopathology. Altogether, these results extend our understanding of the cell- and tissue-specific role that IL-10 exerts in immune regulation. Lay summary: Interleukin-10 is mostly regarded as an immunosuppressive cytokine. We show here that HBV-specific CD8+ T cells produce IL-10 upon antigen recognition and that this cytokine enhances CD8+ T cell survival. As such, IL-10 paradoxically promotes rather than suppresses liver disease. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

U2 - 10.1016/j.jhep.2017.04.020

DO - 10.1016/j.jhep.2017.04.020

M3 - Article

VL - 67

SP - 543

EP - 548

JO - Journal of Hepatology

JF - Journal of Hepatology

SN - 0168-8278

IS - 3

ER -