| Literature DB >> 16618603 |
Manling Zhang1, Sun-Mi Park, Yue Wang, Ramila Shah, Ni Liu, Andrea E Murmann, Chyung-Ru Wang, Marcus E Peter, Philip G Ashton-Rickardt.
Abstract
How cytotoxic T lymphocytes (CTLs) kill intracellular pathogens without killing themselves has been a recurring question ever since their discovery. By using mice deficient in Serine Protease Inhibitor 6 (Spi6), we show that by inhibiting granzyme B (GrB), Spi6 protects CTLs from self-inflicted injury. Infection with either Lymphocytic Choriomeningitis virus (LCMV) or Listeria monocytogenes (LM) revealed increased apoptosis and diminished survival of Spi6 knockout (KO) CTLs, which was cell autonomous and could be corrected by GrB deficiency. Spi6 KO mice in turn were impaired in their ability to clear LCMV infection. Spi6 KO CTLs revealed a breakdown in the integrity of cytotoxic granules, increased cytoplasmic GrB, and ensuing apoptosis. We conclude that Spi6 protects CTLs from suicide caused by GrB-mediated breakdown of cytotoxic granules.Entities:
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Year: 2006 PMID： 16618603 DOI： 10.1016/j.immuni.2006.02.002
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 31.745