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How dendritic cells (DC) present Ag to cytotoxic T cells (CTL) without themselves being killed through contact-mediated cytotoxicity (so-called kiss of death) has proved to be controversial. Using mice deficient in serine protease inhibitor 6 (Spi6), we show that Spi6 protects DC from the kiss of death by inhibiting granzyme B (GrB) delivered by CTL. Infection of Spi6 knockout mice with lymphocytic choriomeningitis virus revealed impaired survival of CD8α DC. The impaired survival of Spi6 knockout CD8α DC resulted in impaired priming and expansion of both primary and memory lymphocytic choriomeningitis virus-specific CTL, which could be corrected by GrB deficiency. The rescue in the clonal burst obtained by GrB elimination demonstrated that GrB was the physiological target through which Spi6 protected DC from CTL. We conclude that the negative regulation of DC priming of CD8 T lymphocyte immunity by CTL killing is mitigated by the physiological inhibition of GrB by Spi6.

Original publication

DOI

10.4049/jimmunol.1102667

Type

Journal article

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Date

02/2012

Volume

188

Pages

1057 - 1063

Addresses

Section of Immunobiology, Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Imperial College London, London W12 0NN, United Kingdom.

Keywords

Dendritic Cells, CD8-Positive T-Lymphocytes, T-Lymphocytes, Cytotoxic, Animals, Mice, Knockout, Mice, Serine Endopeptidases, Membrane Proteins, Serpins, Serine Proteinase Inhibitors, Cytotoxicity, Immunologic, Antigen Presentation, Granzymes