title: Delta1-Notch3 interactions bias the functional differentiation of activated CD4+ T cells.
abstract: Following activation by antigen, naive CD4+ T helper precursor cells execute distinct genetic programs that result in their differentiation toward the type 1 or type 2 helper T cell (Th1 or Th2) phenotype. Although the differentiation and function of these Th subsets has been well studied, little is known about the contribution to these differentiation events of cell surface receptors other than those for soluble cytokines, such as IL-12 or IL-4. Here, we provide direct evidence that the Delta1 interaction with Notch3 on CD4+ T cells transduces signals, promoting development toward the Th1 phenotype. The positive role of Notch signaling in effector cell differentiation was dose dependent, with high levels of stimulation resulting in reduced T cell activation. Our data revealed a clear contribution of Notch pathways to Th1 versus Th2 fate decisions, while also providing insight into another mechanism for inhibition of CD4+ T cell activation.
authors.affiliation: Department of Immunology & Parasitology, School of Medicine, The University of Tokushima, Tokushima 770-8503, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Maekawa
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Tsukumo
authors.forename: Shigeru
authors.initials: S
authors.lastname: Chiba
authors.forename: Hisamaru
authors.initials: H
authors.lastname: Hirai
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Okada
authors.forename: Kenji
authors.initials: K
authors.lastname: Kishihara
authors.forename: Koji
authors.initials: K
authors.lastname: Yasutomo
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D007371:Interferon-gamma / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D018320:Leishmania major / Q000472:pathogenicity; D016773:Leishmaniasis, Cutaneous / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D000071656:Receptor, Notch3; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D020825:T-Box Domain Proteins; D014157:Transcription Factors / Q000378:metabolism; D000098815:T-bet Transcription Factor
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C499373:Notch3 protein, mouse; D011518:Proto-Oncogene Proteins; D000071656:Receptor, Notch3; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; C064045:delta protein; C073572:Notch4 protein, mouse; D007371:Interferon-gamma