title: CD226 (DNAM-1) is involved in lymphocyte function-associated antigen 1 costimulatory signal for naive T cell differentiation and proliferation.
abstract: Upon antigen recognition by the T cell receptor, lymphocyte function-associated antigen 1 (LFA-1) physically associates with the leukocyte adhesion molecule CD226 (DNAM-1) and the protein tyrosine kinase Fyn. We show that lentiviral vector-mediated mutant (Y-F322) CD226 transferred into naive CD4+ helper T cells (Ths) inhibited interleukin (IL)-12-independent Th1 development initiated by CD3 and LFA-1 ligations. Moreover, proliferation induced by LFA-1 costimulatory signal was suppressed in mutant (Y-F322) CD226-transduced naive CD4+ and CD8+ T cells in the absence of IL-2. These results suggest that CD226 is involved in LFA-1-mediated costimulatory signals for triggering naive T cell differentiation and proliferation. We also demonstrate that although LFA-1, CD226, and Fyn are polarized at the immunological synapse upon stimulation with anti-CD3 in CD4+ and CD8+ T cells, lipid rafts are polarized in CD4+, but not CD8+, T cells. Moreover, proliferation initiated by LFA-1 costimulatory signal is suppressed by lipid raft disruption in CD4+, but not CD8+, T cells, suggesting that the LFA-1 costimulatory signal is independent of lipid rafts in CD8+ T cells.
authors.affiliation: Laboratory for Immune Receptor, RIKEN Research Center for Allergy and Immunology, 3-1-1 Koyadai, Ibaraki 305-0074, Japan. ashibuya@rtc.riken.go.jp
authors.forename: Kazuko
authors.initials: K
authors.lastname: Shibuya
authors.forename: Jun
authors.initials: J
authors.lastname: Shirakawa
authors.forename: Tomie
authors.initials: T
authors.lastname: Kameyama
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Honda
authors.forename: Satoko
authors.initials: S
authors.lastname: Tahara-Hanaoka
authors.forename: Akitomo
authors.initials: A
authors.lastname: Miyamoto
authors.forename: Masafumi
authors.initials: M
authors.lastname: Onodera
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sumida
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Nakauchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyoshi
authors.forename: Akira
authors.initials: A
authors.lastname: Shibuya
mesh_terms: D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D002454:Cell Differentiation; D002455:Cell Division; D022761:Gene Transfer, Horizontal; D005822:Genetic Vectors; D006801:Humans; D018664:Interleukin-12 / Q000502:physiology; D007376:Interleukin-2 / Q000494:pharmacology; D016086:Lentivirus / Q000235:genetics; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D021962:Membrane Microdomains / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*; D018417:Th1 Cells / Q000502:physiology; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D018664:Interleukin-12