iMATEs – A successful immunotherapy against chronic viral infection
Chronic liver infections are difficult to overcome due to mechanisms that limit the function and population expansion of cytotoxic effector CD8+ T cells (cytotoxic T lymphocytes (CTLs)). This limitation may protect the infected liver from overwhelming immunopathology by inducing oscillatory CTL effector function but may also functionally compromise pathogen-specific CTLs. However, large numbers of parasite-specific CTLs are needed to eradicate infected hepatocytes.
A new therapeutic vaccination strategy could solve the problem by using Toll-like receptor ligands as an unspecific enhancer: The induction of intrahepatic myeloid cell aggregates through application of Toll-like receptor 9 agonist (TLR9 ligand) enables massive expansion of the CTL population locally in the liver. The intrahepatic myeloid-cell aggregates for T cell population expansion (iMATEs) are rapidly formed within 2d after TLR9 signaling and provide a nonperfused cocoon-like anatomic structure for local CTL proliferation. Thus, such population expansion of CTLs in the liver controls acute and chronic viral infection of the liver and can eradicate chronic viral infection
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