Notch regulates cytolytic effector function in CD8+ T cells

Ok Hyun Cho, Hyun Mu Shin, Lucio Miele, Todd E. Golde, Abdul Fauq, Lisa M. Minter, Barbara A. Osborne

Research output: Contribution to journalArticlepeer-review

110 Scopus citations

Abstract

The 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.

Original languageEnglish
Pages (from-to)3380-3389
Number of pages10
JournalJournal of Immunology
Volume182
Issue number6
DOIs
StatePublished - 15 Mar 2009
Externally publishedYes

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