Immunosurveillance of the liver by intravascular effector CD8+ T cells

Luca G. Guidotti; Donato Inverso; Laura Sironi; Pietro Di Lucia; Jessica Fioravanti; Lucia Ganzer; Amleto Fiocchi; Maurizio Vacca; Roberto Aiolfi; Stefano Sammicheli; Marta Mainetti; Tiziana Cataudella; Andrea Raimondi; Gloria Gonzalez-Aseguinolaza; Ulrike Protzer; Zaverio M. Ruggeri; Francis V. Chisari; Masanori Isogawa; Giovanni Sitia; Matteo Iannacone

doi:10.1016/j.cell.2015.03.005

Immunosurveillance of the liver by intravascular effector CD8+ T cells

Luca G. Guidotti
, Donato Inverso
, Laura Sironi
, Pietro Di Lucia
, Jessica Fioravanti
, Lucia Ganzer
, Amleto Fiocchi
, Maurizio Vacca
, Roberto Aiolfi
, Stefano Sammicheli
, Marta Mainetti
, Tiziana Cataudella
, Andrea Raimondi
, Gloria Gonzalez-Aseguinolaza
, Ulrike Protzer
, Zaverio M. Ruggeri
, Francis V. Chisari
, Masanori Isogawa
, Giovanni Sitia
, Matteo Iannacone

Chair of Virology

Istituto Scientifico San Raffaele
Scripps Research Institute
University Vita-Salute San Raffaele
Universit̀ Degli Studi di Milano-Bicocca
Center for Applied Medical Research

Research output: Contribution to journal › Article › peer-review

287 Scopus citations

Abstract

Effector CD8⁺ T cells (CD8 T_E) play a key role during hepatotropic viral infections. Here, we used advanced imaging in mouse models of hepatitis B virus (HBV) pathogenesis to understand the mechanisms whereby these cells home to the liver, recognize antigens, and deploy effector functions. We show that circulating CD8 T_E arrest within liver sinusoids by docking onto platelets previously adhered to sinusoidal hyaluronan via CD44. After the initial arrest, CD8 T_E actively crawl along liver sinusoids and probe sub-sinusoidal hepatocytes for the presence of antigens by extending cytoplasmic protrusions through endothelial fenestrae. Hepatocellular antigen recognition triggers effector functions in a diapedesis-independent manner and is inhibited by the processes of sinusoidal defenestration and capillarization that characterize liver fibrosis. These findings reveal the dynamic behavior whereby CD8 T_E control hepatotropic pathogens and suggest how liver fibrosis might reduce CD8 T_E immune surveillance toward infected or transformed hepatocytes.

Original language	English
Pages (from-to)	486-500
Number of pages	15
Journal	Cell
Volume	161
Issue number	3
DOIs	https://doi.org/10.1016/j.cell.2015.03.005
State	Published - 23 Apr 2015

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SDG 3 Good Health and Well-being

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10.1016/j.cell.2015.03.005

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Guidotti, L. G., Inverso, D., Sironi, L., Di Lucia, P., Fioravanti, J., Ganzer, L., Fiocchi, A., Vacca, M., Aiolfi, R., Sammicheli, S., Mainetti, M., Cataudella, T., Raimondi, A., Gonzalez-Aseguinolaza, G., Protzer, U., Ruggeri, Z. M., Chisari, F. V., Isogawa, M., Sitia, G., & Iannacone, M. (2015). Immunosurveillance of the liver by intravascular effector CD8+ T cells. Cell, 161(3), 486-500. https://doi.org/10.1016/j.cell.2015.03.005

@article{071aa314cae349e88c564743e792c382,

title = "Immunosurveillance of the liver by intravascular effector CD8+ T cells",

abstract = "Effector CD8+ T cells (CD8 TE) play a key role during hepatotropic viral infections. Here, we used advanced imaging in mouse models of hepatitis B virus (HBV) pathogenesis to understand the mechanisms whereby these cells home to the liver, recognize antigens, and deploy effector functions. We show that circulating CD8 TE arrest within liver sinusoids by docking onto platelets previously adhered to sinusoidal hyaluronan via CD44. After the initial arrest, CD8 TE actively crawl along liver sinusoids and probe sub-sinusoidal hepatocytes for the presence of antigens by extending cytoplasmic protrusions through endothelial fenestrae. Hepatocellular antigen recognition triggers effector functions in a diapedesis-independent manner and is inhibited by the processes of sinusoidal defenestration and capillarization that characterize liver fibrosis. These findings reveal the dynamic behavior whereby CD8 TE control hepatotropic pathogens and suggest how liver fibrosis might reduce CD8 TE immune surveillance toward infected or transformed hepatocytes.",

author = "Guidotti, \{Luca G.\} and Donato Inverso and Laura Sironi and \{Di Lucia\}, Pietro and Jessica Fioravanti and Lucia Ganzer and Amleto Fiocchi and Maurizio Vacca and Roberto Aiolfi and Stefano Sammicheli and Marta Mainetti and Tiziana Cataudella and Andrea Raimondi and Gloria Gonzalez-Aseguinolaza and Ulrike Protzer and Ruggeri, \{Zaverio M.\} and Chisari, \{Francis V.\} and Masanori Isogawa and Giovanni Sitia and Matteo Iannacone",

note = "Publisher Copyright: {\textcopyright}2015 Elsevier Inc.",

year = "2015",

month = apr,

day = "23",

doi = "10.1016/j.cell.2015.03.005",

language = "English",

volume = "161",

pages = "486--500",

journal = "Cell",

issn = "0092-8674",

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Guidotti, LG, Inverso, D, Sironi, L, Di Lucia, P, Fioravanti, J, Ganzer, L, Fiocchi, A, Vacca, M, Aiolfi, R, Sammicheli, S, Mainetti, M, Cataudella, T, Raimondi, A, Gonzalez-Aseguinolaza, G, Protzer, U, Ruggeri, ZM, Chisari, FV, Isogawa, M, Sitia, G & Iannacone, M 2015, 'Immunosurveillance of the liver by intravascular effector CD8+ T cells', Cell, vol. 161, no. 3, pp. 486-500. https://doi.org/10.1016/j.cell.2015.03.005

TY - JOUR

T1 - Immunosurveillance of the liver by intravascular effector CD8+ T cells

AU - Guidotti, Luca G.

AU - Inverso, Donato

AU - Sironi, Laura

AU - Di Lucia, Pietro

AU - Fioravanti, Jessica

AU - Ganzer, Lucia

AU - Fiocchi, Amleto

AU - Vacca, Maurizio

AU - Aiolfi, Roberto

AU - Sammicheli, Stefano

AU - Mainetti, Marta

AU - Cataudella, Tiziana

AU - Raimondi, Andrea

AU - Gonzalez-Aseguinolaza, Gloria

AU - Protzer, Ulrike

AU - Ruggeri, Zaverio M.

AU - Chisari, Francis V.

AU - Isogawa, Masanori

AU - Sitia, Giovanni

AU - Iannacone, Matteo

PY - 2015/4/23

Y1 - 2015/4/23

N2 - Effector CD8+ T cells (CD8 TE) play a key role during hepatotropic viral infections. Here, we used advanced imaging in mouse models of hepatitis B virus (HBV) pathogenesis to understand the mechanisms whereby these cells home to the liver, recognize antigens, and deploy effector functions. We show that circulating CD8 TE arrest within liver sinusoids by docking onto platelets previously adhered to sinusoidal hyaluronan via CD44. After the initial arrest, CD8 TE actively crawl along liver sinusoids and probe sub-sinusoidal hepatocytes for the presence of antigens by extending cytoplasmic protrusions through endothelial fenestrae. Hepatocellular antigen recognition triggers effector functions in a diapedesis-independent manner and is inhibited by the processes of sinusoidal defenestration and capillarization that characterize liver fibrosis. These findings reveal the dynamic behavior whereby CD8 TE control hepatotropic pathogens and suggest how liver fibrosis might reduce CD8 TE immune surveillance toward infected or transformed hepatocytes.

AB - Effector CD8+ T cells (CD8 TE) play a key role during hepatotropic viral infections. Here, we used advanced imaging in mouse models of hepatitis B virus (HBV) pathogenesis to understand the mechanisms whereby these cells home to the liver, recognize antigens, and deploy effector functions. We show that circulating CD8 TE arrest within liver sinusoids by docking onto platelets previously adhered to sinusoidal hyaluronan via CD44. After the initial arrest, CD8 TE actively crawl along liver sinusoids and probe sub-sinusoidal hepatocytes for the presence of antigens by extending cytoplasmic protrusions through endothelial fenestrae. Hepatocellular antigen recognition triggers effector functions in a diapedesis-independent manner and is inhibited by the processes of sinusoidal defenestration and capillarization that characterize liver fibrosis. These findings reveal the dynamic behavior whereby CD8 TE control hepatotropic pathogens and suggest how liver fibrosis might reduce CD8 TE immune surveillance toward infected or transformed hepatocytes.

UR - https://www.scopus.com/pages/publications/84935488734

U2 - 10.1016/j.cell.2015.03.005

DO - 10.1016/j.cell.2015.03.005

M3 - Article

C2 - 25892224

AN - SCOPUS:84935488734

SN - 0092-8674

VL - 161

SP - 486

EP - 500

JO - Cell

JF - Cell

IS - 3

ER -

Immunosurveillance of the liver by intravascular effector CD8+ T cells

Abstract

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