title: 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.
authors.affiliation: Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA.
authors.forename: Ok Hyun
authors.initials: OH
authors.lastname: Cho
authors.forename: Hyun Mu
authors.initials: HM
authors.lastname: Shin
authors.forename: Lucio
authors.initials: L
authors.lastname: Miele
authors.forename: Todd E
authors.initials: TE
authors.lastname: Golde
authors.forename: Abdul
authors.initials: A
authors.lastname: Fauq
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Minter
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Osborne
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000502:physiology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D053804:Granzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054353:Perforin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D020825:T-Box Domain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: C491198:Eomes protein, mouse; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D020825:T-Box Domain Proteins; D054353:Perforin; D053829:Amyloid Precursor Protein Secretases; D053804:Granzymes