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

6533b7d8fe1ef96bd126af0d

RESEARCH PRODUCT

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

Ulrike Protzer Li-rung Huang Florian Reisinger Craig N. Jenne Hans-peter Dienes Zeinab Abdullah Paul Kubes Nico Van Rooijen Natalio Garbi Margarete Odenthal Edgar Schmitt Michael Croft Frank A. Schildberg Percy A. Knolle Percy A. Knolle Dirk Wohlleber Mathias Heikenwalder Ru-lin Cheng Christian Kurts

subject

T cell medicine.medical_treatment Immunology Population Green Fluorescent Proteins Mice Transgenic Biology CD8-Positive T-Lymphocytes Lymphocytic Choriomeningitis Mice medicine Immunology and Allergy Cytotoxic T cell Animals Lymphocytic choriomeningitis virus Myeloid Cells education Cell Proliferation Mice Knockout education.field_of_study Liver infection CD11b Antigen Microscopy Confocal Liver Diseases Immunotherapy Receptors OX40 Flow Cytometry Mice Inbred C57BL CTL*Chronic infection medicine.anatomical_structure Animals Newborn Liver Toll-Like Receptor 9 Immunology Chronic Disease Host-Pathogen Interactions Immunotherapy CD8 Signal Transduction T-Lymphocytes Cytotoxic

description

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.

year	journal	country	edition	language
2013-01-01	Nature Immunology

10.1038/ni.2573 https://doi.org/10.1038/ni.2573