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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
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter CENTRAL-NERVOUS-SYSTEM; CD8(+) T-CELLS; MYCOBACTERIAL GRANULOMAS; AUTOIMMUNE-DISEASE; EFFECTOR FUNCTION; LYMPHOID ORGAN; ANTIGEN; INFLAMMATION; LYMPHOCYTES; MONOCYTES
ISSN (print) / ISBN 1529-2908
e-ISSN 1529-2916
Zeitschrift Nature Immunology
Quellenangaben Band: 14, Heft: 6, Seiten: 574-583 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)