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Huang, L.R.* ; Wohlleber, D.* ; Reisinger, F. ; Jenne, C.N.* ; Cheng, R.L.* ; Abdullah, Z.* ; Schildberg, F.A.* ; Odenthal, M.* ; Dienes, H.P.* ; van Rooijen, N.* ; Schmitt, E.* ; Garbi, N.* ; Croft, M.* ; Kurts, C.* ; Kubes, P.* ; Protzer, U. ; Heikenwälder, M. ; Knolle, P.A.*

Intrahepatic myeloid-cell aggregates enable local proliferation of CD8+ T cells and successful immunotherapy against chronic viral liver infection.

Nat. Immunol. 14, 574-583 (2013)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Chronic infection is difficult to overcome because of exhaustion or depletion of cytotoxic effector CD8+ T cells (cytotoxic T lymphoytes (CTLs)). Here we report that signaling via Toll-like receptors (TLRs) induced intrahepatic aggregates of myeloid cells that enabled the population expansion of CTLs (iMATEs: 'intrahepatic myeloid-cell aggregates for T cell population expansion') without causing immunopathology. In the liver, CTL proliferation was restricted to iMATEs that were composed of inflammatory monocyte-derived CD11b+ cells. Signaling via tumor-necrosis factor (TNF) caused iMATE formation that facilitated costimulation dependent on the receptor OX40 for expansion of the CTL population. The iMATEs arose during acute viral infection but were absent during chronic viral infection, yet they were still induced by TLR signaling. Such hepatic expansion of the CTL population controlled chronic viral infection of the liver after vaccination with DNA. Thus, iMATEs are dynamic structures that overcome regulatory cues that limit the population expansion of CTLs during chronic infection and can be used in new therapeutic vaccination strategies.
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Publication type Article: Journal article
Document type Scientific Article
Keywords CENTRAL-NERVOUS-SYSTEM; CD8(+) T-CELLS; MYCOBACTERIAL GRANULOMAS; AUTOIMMUNE-DISEASE; EFFECTOR FUNCTION; LYMPHOID ORGAN; ANTIGEN; INFLAMMATION; LYMPHOCYTES; MONOCYTES
Language english
Publication Year 2013
HGF-reported in Year 2013
ISSN (print) / ISBN 1529-2908
e-ISSN 1529-2916
Journal Nature Immunology
Quellenangaben Volume: 14, Issue: 6, Pages: 574-583 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Reviewing status Peer reviewed
Institute(s) Institute of Virology (VIRO)
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30203 - Molecular Targets and Therapies
Research field(s) Immune Response and Infection
PSP Element(s) G-551600-001
G-502700-003
G-502700-004
PubMed ID 23584070
DOI 10.1038/ni.2573
WOS ID WOS:000319107600010
Erfassungsdatum 2013-04-22
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