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Notch regulates cytolytic effector function in CD8+ T cells.

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.

SUBMITTER: Cho OH

PROVIDER: S-EPMC4374745 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Notch regulates cytolytic effector function in CD8+ T cells.

Cho Ok Hyun OH Shin Hyun Mu HM Miele Lucio L Golde Todd E TE Fauq Abdul A Minter Lisa M LM Osborne Barbara A BA

Journal of immunology (Baltimore, Md. : 1950) 20090301 6

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 sh ...[more]

PMID: 19265115

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