Notch regulates cytolytic effector function in CD8+ T cells.

TitleNotch regulates cytolytic effector function in CD8+ T cells.
Publication TypeJournal Article
Year of Publication2009
AuthorsCho OH, Shin HM, Miele L, Golde TE, Fauq A, Minter LM, Osborne BA
JournalJournal of immunology (Baltimore, Md. : 1950)
Volume182
Issue6
Pagination3380-9
Date Published2009 Mar 15
AbstractThe maturation of naive CD8(+) T cells into effector CTLs is a critical feature of a functional adaptive immune system. Development of CTLs depends, in part, upon the expression of the transcriptional regulator eomesodermin (EOMES), which is thought to regulate expression of two key effector molecules, perforin and granzyme B. Although EOMES is important for effector CTL development, the precise mechanisms regulating CD8(+) effector cell maturation remains poorly understood. In this study, we show that Notch1 regulates the expression of EOMES, perforin, and granzyme B through direct binding to the promoters of these crucial effector molecules. By abrogating Notch signaling, both biochemically as well as genetically, we conclude that Notch activity mediates CTL activity through direct regulation of EOMES, perforin, and granzyme B.
Alternate JournalJ. Immunol.