Concomitant type I IFN receptor-triggering of T cells and of DC is required to promote maximal modified vaccinia virus Ankara-induced T-cell expansion

• Published in: European journal of immunology Vol. 40; no. 10; pp. 2769 - 2777
• Main Authors: Frenz, Theresa, Waibler, Zoe, Hofmann, Janin, Hamdorf, Matthias, Lantermann, Markus, Reizis, Boris, Tovey, Michaël G, Aichele, Peter, Sutter, Gerd, Kalinke, Ulrich
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley-VCH Verlag 01-10-2010; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Adoptive Transfer; Animals; Arenaviridae; CD11c Antigen - immunology; CD8+ T‐cell expansion; CD8-Positive T-Lymphocytes - immunology; Dendritic Cells - immunology; Epitopes, T-Lymphocyte; Expansion; Flow Cytometry; Genetic Vectors - immunology; Interferon Type I - immunology; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytic choriomeningitis virus; Mice; Modified vaccinia virus Ankara; Signal Transduction - immunology; T cell receptors; Type I IFN; Vaccinia virus; Vaccinia virus - immunology; Viruses
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201040453

Virus-induced expansion of CD8⁺ T cells may be promoted by type I IFN receptor (IFNAR)-triggering of T cells, depending on the pathogen tested. We studied modified vaccinia virus Ankara (MVA), a promising vaccine vector candidate, which was derived from conventional vaccinia virus (VACV) by more than 570 consecutive in vitro passages. In adoptive transfer experiments, we verified that VACV expressing the gp33 epitope of lymphocytic choriomeningitis virus (VACVgp₃₃) induced largely IFNAR-independent expansion of gp33-specific T cells. On the contrary, MVAgp₃₃-induced T-cell expansion was IFNAR dependent. Interestingly, under the latter conditions, T-cell activation was IFNAR independent, whereas T-cell apoptosis was enhanced in the absence of IFNAR. To address whether MVA-induced T-cell expansion was solely affected by IFNAR-triggering of T cells, expansion of endogenous T cells was studied in conditional mice with a T-cell- or DC-specific IFNAR deletion. Interestingly, both mouse strains showed moderately reduced T-cell expansion, whereas mice with a combined T-cell- and DC-specific IFNAR ablation showed massively reduced T-cell expansion similar to that of IFNAR⁻/⁻ mice. These results are compatible with the model that IFN-inducing viruses such as MVA confer virus-specific CD8⁺ T-cell expansion by concomitant IFNAR-triggering of DC and of T cells.