Serine protease inhibitor 6 protects cytotoxic T cells from self-inflicted injury by ensuring the integrity of cytotoxic granules.

Expression of the Serpin Serine Protease Inhibitor 6 Protects Dendritic Cells from Cytotoxic T Lymphocyte–Induced Apoptosis

Dendritic cells (DCs) play a central role in the immune system as they drive activation of T lymphocytes by cognate interactions. However, as DCs express high levels of major histocompatibility complex class I, this intimate contact may also result in elimination of DCs by activated cytotoxic T lymphocytes (CTLs) and thereby limit induction of immunity. We show here that immature DCs are indeed...

Differential survival of cytotoxic T cells and memory cell precursors.

It is widely assumed that the development of memory CD8 T cells requires the escape of CTLs from programmed cell death. We show in this study that although serine protease inhibitor 6 (Spi6) is required to protect clonal bursts of CTLs from granzyme B-induced programmed cell death, it is not required for the development of memory cells. This conclusion is reached because memory cell precursors ...

Cells from Self-Inflicted Damage Serine Protease Inhibitor 6 Protects iNKT

Serine protease inhibitor 6 is required to protect dendritic cells from the kiss of death.

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 lymphoc...

SPI-CI and SPI-6 cooperate in the protection from effector cell-mediated cytotoxicity.

Tumors have several mechanisms to escape from the immune system. One of these involves expression of intracellular anticytotoxic proteins that modulate the execution of cell death. Previously, we have shown that the serine protease inhibitor (serpin) SPI-6, which inactivates the cytotoxic protease granzyme B (GrB), is capable of preventing cytotoxic T lymphocyte (CTL)-mediated apoptosis. Despit...