Abstract:
: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.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Huang LR,Wohlleber D,Reisinger F,Jenne CN,Cheng RL,Abdullah Z,Schildberg FA,Odenthal M,Dienes HP,van Rooijen N,Schmitt E,Garbi N,Croft M,Kurts C,Kubes P,Protzer U,Heikenwalder M,Knolle PAdoi
10.1038/ni.2573subject
Has Abstractpub_date
2013-06-01 00:00:00pages
574-83issue
6eissn
1529-2908issn
1529-2916pii
ni.2573journal_volume
14pub_type
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