Dendritic Cells Treated with Lipopolysaccharide Up-Regulate Serine Protease Inhibitor 6 and Remain Sensitive to Killing by Cytotoxic T Lymphocytes In Vivo

• Published in: The Journal of immunology (1950) 2008-12, Vol.181 (12), p.8356-8362
• Main Authors: Andrew, Kate A, Simkins, Helen M. A, Witzel, Sabine, Perret, Rachel, Hudson, Jenny, Hermans, Ian F, Ritchie, David S, Yang, Jianping, Ronchese, Franca
• Format: Article
• Language: English
• Subjects: Animals; Cell Death - immunology; Cells, Cultured; Cytotoxicity, Immunologic; Dendritic Cells - enzymology; Dendritic Cells - immunology; Dendritic Cells - transplantation; Immunity, Innate; Lipopolysaccharides - pharmacology; Lymphocyte Activation - immunology; Membrane Proteins - biosynthesis; Membrane Proteins - genetics; Mice; Mice, Inbred C57BL; Mice, Transgenic; NIH 3T3 Cells; Serine Endopeptidases - biosynthesis; Serine Endopeptidases - genetics; Serpins - biosynthesis; Serpins - genetics; T-Lymphocytes, Cytotoxic - cytology; T-Lymphocytes, Cytotoxic - enzymology; T-Lymphocytes, Cytotoxic - immunology; Up-Regulation - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.181.12.8356

Ag presentation by dendritic cells (DC) in vivo is essential to the initiation of primary and secondary T cell responses. We have reported that DC presenting Ag in the context of MHC I molecules also become targets of specific CTL and are rapidly killed in mice. However, activated DC up-regulate expression of serine protease inhibitor (SPI)-6, a specific blocker of the cytotoxic granule protein granzyme B, which modulates their susceptibility to CTL-mediated killing in vitro. We wanted to determine whether susceptibility to CTL-mediated killing in vivo is also modulated by DC activation. As was previously reported by others, DC treated with different doses of LPS expressed higher levels of SPI-6 mRNA than did untreated DC. The increased expression of SPI-6 was functionally relevant, as LPS-treated DC became less susceptible to CTL-mediated killing in vitro. However, when these LPS-treated DC were injected in vivo, they remained sensitive to CTL-mediated killing regardless of whether the CTL activity was elicited in host mice via active immunization or was passively transferred via injection of in vitro-activated CTL. LPS-treated DC were also sensitive to killing in lymph node during the reactivation of memory CTL. We conclude that increased SPI-6 expression is not sufficient to confer DC with resistance to direct killing in vivo. However, SPI-6 expression may provide DC with a survival advantage in some conditions, such as those modeled by in vitro cytotoxicity assays.