title: Transmission of survival signals through Delta-like 1 on activated CD4+T cells.
abstract: Notch expressed on CD4+T cells transduces signals that mediate their effector functions and survival. Although Notch signaling is known to be cis-inhibited by Notch ligands expressed on the same cells, the role of Notch ligands on T cells remains unclear. In this report we demonstrate that the CD4+T cell Notch ligand Dll1 transduces signals required for their survival. Co-transfer of CD4+T cells from Dll1-/-and control mice into recipient mice followed by immunization revealed a rapid decline of CD4+T cells from Dll1-/-mice compared with control cells. Dll1-/-mice exhibited lower clinical scores of experimental autoimmune encephalitis than control mice. The expression of Notch target genes in CD4+T cells from Dll1-/-mice was not affected, suggesting that Dll1 deficiency in T cells does not affect cis Notch signaling. Overexpression of the intracellular domain of Dll1 in Dll1-deficient CD4+T cells partially rescued impaired survival. Our data demonstrate that Dll1 is an independent regulator of Notch-signaling important for the survival of activated CD4+T cells, and provide new insight into the physiological roles of Notch ligands as well as a regulatory mechanism important for maintaining adaptive immune responses.
authors.affiliation: Department of Immunology &Parasitology, Graduate School of Medicine, Tokushima University, Tokushima, Japan.|Department of Clinical Neuroscience, Graduate School of Medicine, Tokushima University, Tokushima, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Furukawa
authors.affiliation: Department of Immunology &Parasitology, Graduate School of Medicine, Tokushima University, Tokushima, Japan.
authors.forename: Chieko
authors.initials: C
authors.lastname: Ishifune
authors.affiliation: Department of Immunology &Parasitology, Graduate School of Medicine, Tokushima University, Tokushima, Japan.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Tsukumo
authors.affiliation: Department of Immunology, Tokai University, Isezaki, Kanagawa, Japan.
authors.forename: Katsuto
authors.initials: K
authors.lastname: Hozumi
authors.affiliation: Department of Immunology &Parasitology, Graduate School of Medicine, Tokushima University, Tokushima, Japan.|Department of Parasitology and Infectious Diseases, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Maekawa
authors.affiliation: Department of Clinical Neuroscience, Graduate School of Medicine, Tokushima University, Tokushima, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Matsui
authors.affiliation: Department of Clinical Neuroscience, Graduate School of Medicine, Tokushima University, Tokushima, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kaji
authors.affiliation: Department of Immunology &Parasitology, Graduate School of Medicine, Tokushima University, Tokushima, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yasutomo