Immunosurveillance of the Liver by Intravascular Effector CD8+ T Cells

被引：253

作者：

Guidotti, Luca G. ^{[1
,2
]}

Inverso, Donato ^{[1
,3
]}

Sironi, Laura ^{[1
,4
]}

Di Lucia, Pietro ^{[1
]}

Fioravanti, Jessica ^{[1
]}

Ganzer, Lucia ^{[1
,4
]}

Fiocchi, Amleto ^{[1
]}

Vacca, Maurizio ^{[1
]}

Aiolfi, Roberto ^{[1
,3
]}

Sammicheli, Stefano ^{[1
]}

Mainetti, Marta ^{[1
]}

Cataudella, Tiziana ^{[1
]}

Raimondi, Andrea ^{[5
]}

Gonzalez-Aseguinolaza, Gloria ^{[6
]}

Protzer, Ulrike ^{[7
]}

Ruggeri, Zaverio M. ^{[8
]}

Chisari, Francis V. ^{[2
]}

Isogawa, Masanori ^{[2
]}

Sitia, Giovanni ^{[1
]}

Iannacone, Matteo ^{[1
,3
,5
]}

机构：

[1] IRCCS San Raffaele Sci Inst, Div Immunol Transplantat & Infect Dis, I-20132 Milan, Italy

[2] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA

[3] Univ Vita Salute San Raffaele, I-20132 Milan, Italy

[4] Univ Milano Bicocca, Dept Phys, I-20126 Milan, Italy

[5] IRCCS San Raffaele Sci Inst, Expt Imaging Ctr, I-20132 Milan, Italy

[6] Ctr Appl Med Res, Gene Therapy & Gene Regulat Program, Pamplona 31008, Spain

[7] Tech Univ Munich, Inst Virol, D-81675 Munich, Germany

[8] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA

来源：

CELL | 2015年 / 161卷 / 03期

基金：

欧洲研究理事会;

关键词：

VIRUS; PLATELETS; MIGRATION; HYALURONAN; GENERATION; CLEARANCE; NETWORKS; DYNAMICS; ENTRY; CD44;

D O I：

10.1016/j.cell.2015.03.005

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：486 / 500

页数：15

共 34 条

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